Journal articles on the topic 'Β-defensin'
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1
Ryan, Lisa K., Janice Rhodes, Meenakshi Bhat, and Gill Diamond. "Expression of β-Defensin Genes in Bovine Alveolar Macrophages." Infection and Immunity 66, no. 2 (February 1, 1998): 878–81. http://dx.doi.org/10.1128/iai.66.2.878-881.1998.
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ABSTRACT Bovine alveolar macrophages (BAM) were examined for the expression of β-defensins and to determine whether their expression could be upregulated by bacterial lipopolysaccharide (LPS), as observed with β-defensins expressed in bovine tracheal epithelial cells. Four β-defensins were expressed constitutively in BAM, with bovine neutrophil β-defensin (BNBD)-4 and BNBD-5 being the most predominant. This is the first evidence of β-defensin gene expression in a mature myeloid cell. LPS had no effect on β-defensin expression in BAM, even though tumor necrosis factor alpha (TNF-α) production was induced. Nonbacterial inflammatory particles had little effect on β-defensin gene expression or TNF-α production in BAM. We hypothesize that constitutively expressed β-defensins of alveolar macrophages may have a role in lung host defense.
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Tarver, Alan P., Douglas P. Clark, Gill Diamond, John P. Russell, Hediye Erdjument-Bromage, Paul Tempst, Kenneth S. Cohen, et al. "Enteric β-Defensin: Molecular Cloning and Characterization of a Gene with Inducible Intestinal Epithelial Cell Expression Associated with Cryptosporidium parvumInfection." Infection and Immunity 66, no. 3 (March 1, 1998): 1045–56. http://dx.doi.org/10.1128/iai.66.3.1045-1056.1998.
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ABSTRACT A growing body of evidence suggests that endogenous antibiotics contribute to the innate defense of mammalian mucosal surfaces. In the cow, β-defensins constitute a large family of antibiotic peptides whose members have been previously isolated from the respiratory and oral mucosa, as well as circulating phagocytic cells. A novel bovine genomic clone with sequence related to those of these α-defensins was isolated and characterized. The corresponding cDNA was isolated from a small intestinal library; its open reading frame predicts a deduced sequence of a novel β-defensin, which we designate enteric β-defensin (EBD). Northern blot analysis of a variety of bovine tissues revealed that EBD mRNA is highly expressed in the distal small intestine and colon, anatomic locations distinct from those for previously characterized β-defensins. EBD mRNA was further localized by in situ hybridization to epithelial cells of the colon and small intestinal crypts. Infection of two calves with the intestinal parasiteCryptosporidium parvum induced 5- and 10-fold increases above control levels of EBD mRNA in intestinal tissues. An anchored-PCR strategy was used to identify other β-defensin mRNAs expressed in the intestine. In addition to that of EBD, several low-abundance cDNAs which corresponded to other β-defensin mRNAs were cloned. Most of these clones encoded previously characterized β-defensins or closely related isoforms, but two encoded a previously uncharacterized prepro-β-defensin. Northern blot evidence supported that all of these other β-defensin genes are expressed at levels lower than that of the EBD gene in enteric tissue. Furthermore, some of these β-defensin mRNAs were abundant in bone marrow, suggesting that in enteric tissue their expression may be in cells of hematopoietic origin. Extracts of small intestinal mucosa obtained from healthy cows have numerous active chromatographic fractions as determined by an antibacterial assay, and one peptide was partially purified. The peptide corresponded to one of the low-abundance cDNAs. This study provides evidence of β-defensin expression in enteric tissue and that the mRNA encoding a major β-defensin of enteric tissue, EBD, is inducibly expressed in enteric epithelial cells. These findings support the proposal that β-defensins may contribute to host defense of enteric mucosa.
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Yang, D., O. Chertov, S. N. Bykovskaia, Q. Chen, M. J. Buffo, J. Shogan, M. Anderson, et al. "β-Defensins: Linking Innate and Adaptive Immunity Through Dendritic and T Cell CCR6." Science 286, no. 5439 (October 15, 1999): 525–28. http://dx.doi.org/10.1126/science.286.5439.525.
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Defensins contribute to host defense by disrupting the cytoplasmic membrane of microorganisms. This report shows that human β-defensins are also chemotactic for immature dendritic cells and memory T cells. Human β-defensin was selectively chemotactic for cells stably transfected to express human CCR6, a chemokine receptor preferentially expressed by immature dendritic cells and memory T cells. The β-defensin–induced chemotaxis was sensitive to pertussis toxin and inhibited by antibodies to CCR6. The binding of iodinated LARC, the chemokine ligand for CCR6, to CCR6-transfected cells was competitively displaced by β-defensin. Thus, β-defensins may promote adaptive immune responses by recruiting dendritic and T cells to the site of microbial invasion through interaction with CCR6.
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Meade, K. G., P. Cormican, F. Narciandi, A. Lloyd, and C. O'Farrelly. "Bovine β-defensin gene family: opportunities to improve animal health?" Physiological Genomics 46, no. 1 (January 1, 2014): 17–28. http://dx.doi.org/10.1152/physiolgenomics.00085.2013.
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Recent analysis of the bovine genome revealed an expanded suite of β-defensin genes that encode what are referred to as antimicrobial or host defense peptides (HDPs). Whereas primate genomes also encode α- and θ-defensins, the bovine genome contains only the β-defensin subfamily of HDPs. β-Defensins perform diverse functions that are critical to protection against pathogens but also in regulation of the immune response and reproduction. As the most comprehensively studied subclass of HDPs, β-defensins possess the widest taxonomic distribution, found in invertebrates as well as plants, indicating an ancient point of origin. Cross-species comparison of the genomic arrangement of β-defensin gene repertoire revealed them to vary in number among species presumably due to differences in pathogenic selective pressures but also genetic drift. β-Defensin genes exist in a single cluster in birds, but four gene clusters exist in dog, rat, mouse, and cow. In humans and chimpanzees, one of these clusters is split in two as a result of a primate-specific pericentric inversion producing five gene clusters. A cluster of β-defensin genes on bovine chromosome 13 has been recently characterized, and full genome sequencing has identified extensive gene copy number variation on chromosome 27. As a result, cattle have the most diverse repertoire of β-defensin genes so far identified, where four clusters contain at least 57 genes. This expansion of β-defensin HDPs may hold significant potential for combating infectious diseases and provides opportunities to harness their immunological and reproductive functions in commercial cattle populations.
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Patil, Amar A., Yibin Cai, Yongming Sang, Frank Blecha, and Guolong Zhang. "Cross-species analysis of the mammalian β-defensin gene family: presence of syntenic gene clusters and preferential expression in the male reproductive tract." Physiological Genomics 23, no. 1 (September 21, 2005): 5–17. http://dx.doi.org/10.1152/physiolgenomics.00104.2005.
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Mammalian β-defensins are an important family of innate host defense peptides with pleiotropic activities. As a first step to study the evolutionary relationship and biological role of the β-defensin family, we identified their complete repertoires in the human, chimpanzee, mouse, rat, and dog following systemic, genome-wide computational searches. Although most β-defensin genes are composed of two exons separated by an intron of variable length, some contain an additional one or two exons encoding an internal pro-sequence, a segment of carboxy-terminal mature sequences or untranslated regions. Alternatively, spliced isoforms have also been found with several β-defensins. Furthermore, all β-defensin genes are densely clustered in four to five syntenic chromosomal regions, with each cluster spanning <1.2 Mb across the five species. Phylogenetic analysis indicated that, although the majority of β-defensins are evolutionarily conserved across species, subgroups of gene lineages exist that are specific in certain species, implying that some β-defensins originated after divergence of these mammals from each other, while most others arose before the last common ancestor of mammals. Surprisingly, RT-PCR revealed that all but one rat β-defensin transcript are preferentially expressed in the male reproductive tract, particularly in epididymis and testis, except that Defb4, a human β-defensin-2 ortholog, is more restricted to the respiratory and upper gastrointestinal tracts. Moreover, most β-defensins expressed in the reproductive tract are developmentally regulated, with enhanced expression during sexual maturation. Existence of such a vast array of β-defensins in the male reproductive tract suggests that these genes may play a dual role in both fertility and host defense.
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Jia, Hong Peng, Jesse N. Mills, Fariba Barahmand-Pour, Darryl Nishimura, Rama K. Mallampali, Guoshun Wang, Kerry Wiles, Brian F. Tack, Charles L. Bevins, and Paul B. McCray. "Molecular Cloning and Characterization of Rat Genes Encoding Homologues of Human β-Defensins." Infection and Immunity 67, no. 9 (September 1, 1999): 4827–33. http://dx.doi.org/10.1128/iai.67.9.4827-4833.1999.
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ABSTRACT β-Defensins are cationic peptides with broad-spectrum antimicrobial activity that may play a role in mucosal defenses of several organs. They have been isolated in several species, and in humans, two β-defensins have been identified. Here, we report the identification of two genes encoding β-defensin homologues in the rat. Partial cDNAs were found by searching the expressed-sequence-tag database, and primers were designed to generate full-length mRNA coding sequences. One gene was highly similar to the human β-defensin-1 (HBD-1) gene and mouse β-defensin-1 gene at both the nucleic acid and amino acid levels and was termed rat β-defensin-1 (RBD-1). The other gene, named RBD-2, was homologous to the HBD-2 and bovine tracheal antimicrobial peptide (TAP) genes. The predicted prepropeptides were strongly cationic, were 69 and 63 residues in length for RBD-1 and RBD-2, respectively, and contained the six-cysteine motif characteristic of β-defensins. The β-defensin genes mapped closely on rat chromosome 16 and were closely linked to the α-defensins genes, suggesting that they are part of a gene cluster, similar to the organization reported for humans. Northern blot analysis showed that both RBD-1 and RBD-2 mRNA transcripts were ∼0.5 kb in length; RBD-1 mRNA was abundantly transcribed in the rat kidney, while RBD-2 was prevalent in the lung. Reverse transcription-PCR indicated that RBD-1 and RBD-2 mRNAs were distributed in a variety of other tissues. In the lung, RBD-1 mRNA expression localized to the tracheal epithelium while RBD-2 was expressed in alveolar type II cells. In conclusion, we characterized two novel β-defensin homologues in the rat. The rat may be a useful model to investigate the function and contribution of β-defensins to host defense in the lung, kidney, and other tissues.
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Bals, Robert, Mitchell J. Goldman, and James M. Wilson. "Mouse β-Defensin 1 Is a Salt-Sensitive Antimicrobial Peptide Present in Epithelia of the Lung and Urogenital Tract." Infection and Immunity 66, no. 3 (March 1, 1998): 1225–32. http://dx.doi.org/10.1128/iai.66.3.1225-1232.1998.
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ABSTRACT One component of host defense at mucosal surfaces appears to be epithelium-derived peptides with antimicrobial activity called defensins. Human β-defensin 1 (hBD-1) represents the first member of the β-defensin family isolated from humans and has been implicated in the pathogenesis of cystic fibrosis. We describe in this report the isolation and characterization of a murine homolog of hBD-1 called mouse β-defensin 1 (mBD-1). The predicted amino acid sequence shows the hallmark features of other known epithelial β-defensins, including the ordered array of six cysteine residues. Analysis of a genomic clone of mBD-1 revealed two exons separated by a 15-kb intron. By use of fluorescence in situ hybridization, the mBD-1 gene was localized at the proximal portion of chromosome 8, the site where mouse α-defensins are found. Lysates from cells transfected with the mBD-1 cDNA showed antibacterial activity against gram-positive and gram-negative bacteria. mBD-1 transcripts were found in kidney, liver, and female reproductive organ tissues. In the airways, mBD-1 is expressed diffusely throughout the epithelial cells of the large proximal airways with less expression in the small distal airways and no expression in alveolar cells. The present study demonstrates that a β-defensin potentially homologous to human β-defensin 1 is present in the respiratory system and other mucosal surfaces in mice.
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Antcheva, Nikolinka, Francesca Morgera, Luisa Creatti, Lisa Vaccari, Ulrike Pag, Sabrina Pacor, Yechiel Shai, Hans-Georg Sahl, and Alessandro Tossi. "Artificial β-defensin based on a minimal defensin template." Biochemical Journal 421, no. 3 (July 15, 2009): 435–47. http://dx.doi.org/10.1042/bj20082242.
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We have designed and chemically synthesized an artificial β-defensin based on a minimal template derived from the comparative analysis of over 80 naturally occurring sequences. This molecule has the disulfide-bridged β-sheet core structure of natural β-defensins and shows a robust salt-sensitive antimicrobial activity against bacteria and yeast, as well as a chemotactic activity against immature dendritic cells. An SAR (structure–activity relationship) study using two truncated fragments or a Cys→Ser point-mutated analogue, from which one or two of the three disulfide bridges were absent, indicated that altering the structure resulted in a different type of membrane interaction and a switch to different modes of action towards both microbial and host cells, and that covalent dimerization could favour antimicrobial activity. Comparison of the structural, aggregational and biological activities of the artificial defensin with those of three human β-defensins and their primate orthologues provided useful information on how their mode of action may relate to specific structural features.
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Morampudi, Vijay, Michel Y. Braun, and Sushila D'Souza. "Modulation of Early β-Defensin-2 Production as a Mechanism Developed by Type I Toxoplasma gondii To Evade Human Intestinal Immunity." Infection and Immunity 79, no. 5 (March 7, 2011): 2043–50. http://dx.doi.org/10.1128/iai.01086-10.
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ABSTRACTWe investigated the early innate immune responses induced in human intestinal epithelial cells (IEC) by the three definedToxoplasma gondiigenotype strains. Transcriptome analysis revealed that among differentially expressed genes, β-defensins distinguished the most IEC infected by fast- or slow-replicatingT. gondiigenotypes. Although β-defensin 1 and 3 genes were not expressed in host cells at early time points postinfection, the slow-replicating type II and III parasites induced high levels of β-defensin 2 gene expression. Notably, no β-defensin 2 gene expression occurred early after infection with the fast-replicating type I parasite. However, activation of this gene in IEC by poly(I:C) treatment prior to infection substantially decreased parasite viability, and pretreatment of parasites with synthetic β-defensin 2 significantly reduced their infectivity of IEC. These findings strongly support the modulation of early β-defensin 2 expression as a mechanism used by type IT. gondiiparasites to mediate immune evasion.
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Rinker, Sherri D., Michael P. Trombley, Xiaoping Gu, Kate R. Fortney, and Margaret E. Bauer. "Deletion ofmtrCin Haemophilus ducreyi Increases Sensitivity to Human Antimicrobial Peptides and Activates the CpxRA Regulon." Infection and Immunity 79, no. 6 (March 28, 2011): 2324–34. http://dx.doi.org/10.1128/iai.01316-10.
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ABSTRACTHaemophilus ducreyiresists killing by antimicrobial peptides encountered during human infection, including cathelicidin LL-37, α-defensins, and β-defensins. In this study, we examined the role of the proton motive force-dependent multiple transferable resistance (MTR) transporter in antimicrobial peptide resistance inH. ducreyi. We found a proton motive force-dependent effect onH. ducreyi's resistance to LL-37 and β-defensin HBD-3, but not α-defensin HNP-2. Deletion of the membrane fusion protein MtrC renderedH. ducreyimore sensitive to LL-37 and human β-defensins but had relatively little effect on α-defensin resistance. ThemtrCmutant 35000HPmtrCexhibited phenotypic changes in outer membrane protein profiles, colony morphology, and serum sensitivity, which were restored to wild type bytrans-complementation withmtrC. Similar phenotypes were reported in acpxAmutant; activation of the two-component CpxRA regulator was confirmed by showing transcriptional effects on CpxRA-regulated genes in 35000HPmtrC. AcpxRmutant had wild-type levels of antimicrobial peptide resistance; acpxAmutation had little effect on defensin resistance but led to increased sensitivity to LL-37. 35000HPmtrCwas more sensitive than thecpxAmutant to LL-37, indicating that MTR contributed to LL-37 resistance independent of the CpxRA regulon. The CpxRA regulon did not affect proton motive force-dependent antimicrobial peptide resistance; however, 35000HPmtrChad lost proton motive force-dependent peptide resistance, suggesting that the MTR transporter promotes proton motive force-dependent resistance to LL-37 and human β-defensins. This is the first report of a β-defensin resistance mechanism inH. ducreyiand shows that LL-37 resistance inH. ducreyiis multifactorial.
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Zaalouk, Tarek K., Mona Bajaj-Elliott, John T. George, and Vincent McDonald. "Differential Regulation of β-Defensin Gene Expression during Cryptosporidium parvum Infection." Infection and Immunity 72, no. 5 (May 2004): 2772–79. http://dx.doi.org/10.1128/iai.72.5.2772-2779.2004.
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ABSTRACT Invasion of enterocytes by pathogenic microbes evokes both innate and adaptive immune responses, and microbial pathogens have developed strategies to overcome the initial host immune defense. β-Defensins are potentially important endogenous antibiotic-like effectors of innate immunity expressed by intestinal epithelia. In this study, the interplay between the enteric protozoan parasite Cryptosporidium parvum and host epithelial β-defensin expression was investigated. Using human and murine models of infection, we demonstrated that C. parvum infection differentially regulates β-defensin gene expression. Downregulation of murine β-defensin-1 mRNA and protein was observed in both in vitro and in vivo models of infection. Infection of the human colonic HT29 cell line with the parasite resulted in differential effects on various members of the defensin gene family. Partial reduction in human β-defensin-1 (hBD-1), induction of hBD-2, and no effect on hBD-3 gene expression was observed. Recombinant hBD-1 and hBD-2 peptides exhibited significant antimicrobial activity against C. parvum sporozoites in vitro. These findings demonstrate that C. parvum infection of enterocytes may affect the expression of various defensins in different ways and suggest that the overall outcome of the effect of antimicrobial peptides on early survival of the parasite may be complex.
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Estrela, Andreia Bergamo, Manfred Rohde, Maximiliano Gabriel Gutierrez, Gabriella Molinari, and Wolf-Rainer Abraham. "Human β-Defensin 2 Induces Extracellular Accumulation of Adenosine in Escherichia coli." Antimicrobial Agents and Chemotherapy 57, no. 9 (July 1, 2013): 4387–93. http://dx.doi.org/10.1128/aac.00820-13.
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ABSTRACTHuman β-defensins are host defense peptides performing antimicrobial as well as immunomodulatory functions. The present study investigated whether treatment ofEscherichia coliwith human β-defensin 2 could generate extracellular molecules of relevance for immune regulation. Mass spectrometry analysis of bacterial supernatants detected the accumulation of purine nucleosides triggered by β-defensin 2 treatment. Other cationic antimicrobial peptides tested presented variable outcomes with regard to extracellular adenosine accumulation; human β-defensin 2 was the most efficient at inducing this response. Structural and biochemical evidence indicated that a mechanism other than plain lysis was involved in the observed phenomenon. By use of isotope (13C) labeling, extracellular adenosine was found to be derived from preexistent RNA, and a direct interaction between the peptide and bacterial nucleic acid was documented for the first time for β-defensin 2. Taken together, the data suggest that defensin activity on a bacterial target may alter local levels of adenosine, a well-known immunomodulator influencing inflammatory processes.
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Lysenko, K. I. "COMPARATIVE ASSESSMENT OF β-DEFENSIN LEVELS IN PATIENTS WITH CHRONIC ECZEMA OF VARYING SEVERITY." International Medical Journal, no. 3 (September 16, 2020): 67–71. http://dx.doi.org/10.37436/2308-5274-2020-3-13.
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The infectious nature of the process in microbial eczema or complications of bacterial infection of true eczema indicates an impairment in the immune system, especially innate immunity. Primary pathogen receptors, the complement system, phagocytosis, interferons, and endogenous antibiotic peptides play a crucial role in the body's innate defense. The first line of defense is provided by antimicrobial peptides, which are non−specific factors of humoral immunity, and have endotoxin−neutralizing and immune modulatory activity, as well as act against a wide range of microorganisms. One of them is defensins, which are cationic amphipathic peptides with a length of 30 to 42 amino acids with a three−stranded β−plate structure containing three disulfide bonds. The main producers of human β−defensins (Human Beta Defensin) are various epithelial cells, including keratinocytes. Defensins have antibacterial, antiviral, antifungal and antiparasitic effects. β−defensins are active against gram−positive and gram−negative bacteria, in addition, they exhibit anti−yeast activity. In patients, the severity of dermatosis was determined based on the calculation of EASI (Eczema Area Severity Index), the content of Human Beta Defensin was done with enzyme−linked immunosorbent assay, in the serum of patients with chronic eczema, it was increased 15.9 times compared to the control group. Quantitative levels of Human Beta Defensin 2 have been shown to be closely related to the disease severity. The content of Human Beta Defensin 2 in the serum of patients with chronic eczema may be a marker of the dermatosis severity. Key words: chronic eczema, true and microbial eczema, pathogenesis, β−defensin, severity.
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Narciandi, F., A. Lloyd, K. G. Meade, and C. O'Farrelly. "A novel subclass of bovine β-defensins links reproduction and immunology." Reproduction, Fertility and Development 26, no. 6 (2014): 769. http://dx.doi.org/10.1071/rd13153.
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β-defensins are effector molecules of the innate immune system, found in many diverse species. Their presence in invertebrates as well as vertebrates suggests highly conserved functional roles. Most β-defensins are believed to act as antimicrobial agents at epithelial surfaces, although additional functions have also been described, including immune regulatory activity, wound repair and a role in coat-colour determination. High expression of β-defensins have been found in testis and epididymidal epithelium as well as in the seminal fluid of humans, macaque, rat, mouse and cow. Human and macaque β-defensins have recently been shown to affect sperm motility while a mutation in β-defensin 126 is associated with reduced fertility in men. Genetic variation in bovine defensin genes may explain the increased incidence of low fertility in cattle. Here, we present a summary of the known functions of β-defensins as well as their emerging role in reproduction and their potential to improve fertility in cattle.
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Kamilova, A. T., D. I. Akhmedova, Z. E. Umarnazarova, D. A. Abdullaeva, and S. I. Geller. "Concentration of fecal β-defensin-2 in children with cystic fibrosis: how the inneral intestinal immune response?" Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) 66, no. 6 (January 20, 2022): 71–76. http://dx.doi.org/10.21508/1027-4065-2021-66-6-71-76.
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Cystic fibrosis is a disease caused by mutations in a gene encoding CFTR-protein (Cystic Fibrosis Transmembrane conductance Regulator), located in the apical membrane of epithelial cells of the respiratory tract, intestines and pancreas. Defensins serve as important components of the innate human immune system, they play a key role in providing the first line of defense of a macroorganism against infection; they have high antimicrobial, antiviral, cytotoxic activity.Objective. To determine the values of fecal β-defensin-2 in children with cystic fibrosis and to reveal the dependence of its level on the exocrine function of the pancreas and the severity of the patient’s condition.Characteristics of children and research methods. The study included 57 children with cystic fibrosis, the average age was 20.93 ± 2.9 months. Cystic fibrosis was diagnosed on the basis of an increase in immunoreactive trypsin, sweat chlorides by Cook’s method (>60 meq / l). To assess the exocrine function of the pancreas the scientists determined the activity of fecal elastase. They evaluated the levels of fecal β-defensin-2 and calprotectin using a quantitative enzyme immunoassay.Results. The levels of fecal β-defensin-2 were increased (108.2 ± 11.3 ng / ml) in all children under examination. The researchers found no correlation between the levels of fecal β-defensin-2 and fecal elastase. The level of fecal calprotectin was significantly higher in the group of children with cystic fibrosis as compared to the control group. There was a significant correlation between the levels of fecal calprotectin and fecal β-defensin-2 (r=0.57; p <0.05), however, no correlations were found between the levels of fecal β-defensin-2 and fecal elastase. The group of children with a severe course of the disease demonstrated an increase in the level of fecal β-defensin-2, fecal calprotectin significantly more frequent.Conclusion. Children with cystic fibrosis demonstrated a significant increase in the concentration of β-defensin-2 as compared to the control group, which confirms the activation of the innate immune system of the intestinal mucosa. The researchers traced the relationship between high levels of fecal β-defensin-2 and the severity of the disease. The levels of fecal β-defensin-2 directly correlated with the concentration of fecal calprotectin and there was no correlation between the severity of pancreatic insufficiency and the concentration of fecal β-defensin-2.
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Xiao, Li-Qing, Ai-Hua Liu, and Yong-Lian Zhang. "An Effective Method for Raising Antisera Against β-defensins: Double-copy Protein Expression of mBin1b in E. coli." Acta Biochimica et Biophysica Sinica 36, no. 8 (August 1, 2004): 571–76. http://dx.doi.org/10.1093/abbs/36.8.571.
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Abstract Bin1b is a rat epididymis specific β-defensin which may have fertility related functions in addition to its antimicrobial activity. β-defensins are cysteine-rich cationic antimicrobial peptides that have their important implications in innate and adaptive immunity. Though considerable numbers of new β-defensins have been discovered, few corresponding antibodies have been reported. The small peptide with special structure and antimicrobial nature of β-defensins make them very difficult to express in prokaryotic system. Here we adopted a double-copy protein expression scheme based on which not only the mBin1b protein was successfully expressed but also the immunity of the antigen was enhanced. The validity of the antisera was verified by using Western blotting and immunohistochemical analyses. It will be a useful tool for deeply investigating the roles of Bin1b and also provide a simple but effective method in raising antisera against other members of the β-defensin gene family.
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Huang, Juan, Junhui Li, Qiufen Li, Lin Li, Nianhua Zhu, Xiaowen Xiong, and Guanhong Li. "Peptidoglycan derived from Lactobacillus rhamnosus MLGA up-regulates the expression of chicken β-defensin 9 without triggering an inflammatory response." Innate Immunity 26, no. 8 (August 26, 2020): 733–45. http://dx.doi.org/10.1177/1753425920949917.
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Defensins are critical components of the innate immune system and play an important role in the integration of innate and adaptive immune responses. Although information on the immunomodulatory properties of peptidoglycan from bacteria is abundant, little is known about the β-defensin induction effect of peptidoglycan from the probiotic Lactobacillus. This study investigated the effect of intact peptidoglycan from L. rhamnosus MLGA on the induction of avian β-defensin 9 in chicken immune cells and intestinal explants. Peptidoglycan from Lactobacillus rhamnosus MLGA dose dependently promoted avian β-defensin 9 mRNA expression in chicken PBMCs, splenocytes, thymocytes, hepatocytes, and chicken embryo jejunum, ileum, and cecum explants and increased the capacity of PBMC or splenocyte lysates to inhibit the growth of Salmonella Enteritidis. In contrast to the effect of L. rhamnosus MLGA-derived peptidoglycan, peptidoglycan derived from pathogenic Staphylococcus aureus reduced avian β-defensin 9 mRNA expression in chicken PBMCs and splenocytes. The inducible effect of peptidoglycan from L. rhamnosus MLGA on avian β-defensin 9 expression in PBMCs and splenocytes was observed without activation of the expression of associated pro-inflammatory cytokines IL-1β, IL-8, and IL-12p40, whereas these cytokine expressions were suppressed by peptidoglycan hydrolysate obtained by lysozyme digestion. The results of the present study show the capability of peptidoglycan derived from L. rhamnosus MLGA to induce the antimicrobial peptide defensin while simultaneously avoiding the deleterious risks of an inflammatory response.
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Mathews, Michael, Hong Peng Jia, Janet M. Guthmiller, Garrett Losh, Scott Graham, Georgia K. Johnson, Brian F. Tack, and Paul B. McCray. "Production of β-Defensin Antimicrobial Peptides by the Oral Mucosa and Salivary Glands." Infection and Immunity 67, no. 6 (June 1, 1999): 2740–45. http://dx.doi.org/10.1128/iai.67.6.2740-2745.1999.
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ABSTRACT β-Defensins are cationic peptides with broad-spectrum antimicrobial activity that are produced by epithelia at mucosal surfaces. Two human β-defensins, HBD-1 and HBD-2, were discovered in 1995 and 1997, respectively. However, little is known about the expression of HBD-1 or HBD-2 in tissues of the oral cavity and whether these proteins are secreted. In this study, we characterized the expression of HBD-1 and HBD-2 mRNAs within the major salivary glands, tongue, gingiva, and buccal mucosa and detected β-defensin peptides in salivary secretions. Defensin mRNA expression was quantitated by RNase protection assays. HBD-1 mRNA expression was detected in the gingiva, parotid gland, buccal mucosa, and tongue. Expression of HBD-2 mRNA was detected only in the gingival mucosa and was most abundant in tissues with associated inflammation. To test whether β-defensin expression was inducible, gingival keratinocyte cell cultures were treated with interleukin-1β (IL-1β) or bacterial lipopolysaccharide (LPS) for 24 h. HBD-2 expression increased ∼16-fold with IL-1β treatment and ∼5-fold in the presence of LPS. Western immunoblotting, liquid chromatography, and mass spectrometry were used to identify the HBD-1 and HBD-2 peptides in human saliva. Human β-defensins are expressed in oral tissues, and the proteins are secreted in saliva; HBD-1 expression was constitutive, while HBD-2 expression was induced by IL-1β and LPS. Human β-defensins may play an important role in the innate defenses against oral microorganisms.
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Prahl, Adam, Marzena Pazgier, Jerry Alexandratos, and Jacek Lubkowski. "Human β-defensin 4 – defensin without the “twist”." Postępy Biochemii 62, no. 3 (November 15, 2016): 349–61. http://dx.doi.org/10.18388/pb.2016_36.
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β-defensins are small, cysteine-rich, cationic peptides that contribute to various processes related to both arms of host defense, the innate and adaptive immunities. All β-defensins are potent antimicrobials with activity targeting a broad range of pathogens. Some human β-defensins (hBDs) are also capable of binding and activating specific chemokine receptors, leading to chemotaxis of receptor-presenting cells. Two receptors identified as targets of specific human β-defensins are CCR2 and CCR6, both members of the seven-transmembrane family of chemokine receptors. Currently, around 50 open reading frames (ORFs) identified in the human genome encode proteins that have signatures characteristic of β-defensins. Of those, only three, hBD1-3, have been thoroughly characterized to date, including a detailed structural description of their molecules. In addition, limited information on biological and bactericidal properties is available for hBD4, as well as the solution structure of hBD6. The crystal structure of hBD4, determined here at resolution of 1.60 Å, indicates significant structural differences between this molecule and those reported previously for other hBDs. Crystallographic studies indicate a possibility of unique dimerization of hBD4, confirmed by solution studies using analytical ultracentrifugation. In contrast to hBD1-3, hBD4 does not induce CCR6-mediated chemotaxis. This observation can be attributed to an unusual conformation of the hBD4 N-terminus. In agreement with previously published reports, hBD4 was shown to be a potent antibacterial agent, as demonstrated by results of assays with E. coli ATCC 25922 cells.
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Shelburne, Charles E., Wilson A. Coulter, De'Avlin Olguin, Marilyn S. Lantz, and Dennis E. Lopatin. "Induction of β-Defensin Resistance in the Oral Anaerobe Porphyromonas gingivalis." Antimicrobial Agents and Chemotherapy 49, no. 1 (January 2005): 183–87. http://dx.doi.org/10.1128/aac.49.1.183-187.2005.
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ABSTRACT Induction of resistance of oral anaerobes to the effects of human β-defensin 1 (hβD-1) to hβD-4 was investigated by pretreating cells with either sublethal levels of defensins or environmental factors, followed by a challenge with lethal levels of defensins. Cultures of Porphyromonas gingivalis were (i) pretreated with defensins at 1 ng/ml, (ii) heated to 42°C (heat stress), (iii) exposed to normal atmosphere (oxidative stress), or (iv) exposed to 1 mM hydrogen peroxide (peroxide stress). Samples (10 μl) were distributed among the wells of sterile 384-well plates containing hβD-1 to -4 (100 μg/ml). Plates were incubated at 37°C for 36 h in an anaerobe chamber. Growth inhibition was determined by a system that measures the total nucleic acid of a sample with a DNA binding dye. The MICs of the four defensins for P. gingivalis were 3 to 12 μg/ml. We found that sublethal levels of the defensins and heat and peroxide stress, but not oxidative stress, induced resistance to 100 μg of defensin per ml in P. gingivalis. Resistance induced by sublethal levels of hβD-2 lasted 90 min, and the resistance induced by each defensin was effective against the other three. Multiple strains exposed to hβD-2 all evidenced resistance induction. Defensin resistance is vital to the pathogenic potential of several human pathogens. This is the first report describing the induction of defensin resistance in the oral periodontal pathogen P. gingivalis. Such resistance may have an effect on the ability of oral pathogens to persist in the mouth and to withstand innate human immunity.
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Derache, Chrystelle, Valérie Labas, Vincent Aucagne, Hervé Meudal, Céline Landon, Agnès F. Delmas, Thierry Magallon, and Anne-Christine Lalmanach. "Primary Structure and Antibacterial Activity of Chicken Bone Marrow-Derived β-Defensins." Antimicrobial Agents and Chemotherapy 53, no. 11 (September 8, 2009): 4647–55. http://dx.doi.org/10.1128/aac.00301-09.
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ABSTRACTThree biologically active β-defensins were purified by chromatography from chicken bone marrow extract: avian β-defensin 1 (AvBD1), AvBD2, and the newly isolated β-defensin AvBD7. Mass spectrometry analyses showed that bone marrow-derived AvBD1, -2, and -7 peptides were present as mature peptides and revealed posttranslational modifications for AvBD1 and AvBD7 in comparison to their in silico-predicted amino acid sequences. Tandem mass spectrometry analysis using the nanoelectrospray-quadrupole time of flight method showed N-terminal glutaminyl cyclization of mature AvBD7 and C-terminal amidation of mature AvBD1 peptide, while posttranslational modifications were absent in bone marrow-derived mature AvBD2 peptide. Furthermore, mass spectrometry analysis performed on intact cells confirmed the presence of these three peptides in mature heterophils. In addition, the antibacterial activities of the three β-defensins against a large panel of gram-positive and -negative bacteria were assessed. While the three defensins displayed similar antibacterial spectra of activity against gram-positive strains, AvBD1 and AvBD7 exhibited the strongest activity against gram-negative strains in comparison to AvBD2.
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Guyot, Nicolas, Hervé Meudal, Sascha Trapp, Sophie Iochmann, Anne Silvestre, Guillaume Jousset, Valérie Labas, et al. "Structure, function, and evolution ofGga-AvBD11, the archetype of the structural avian-double-β-defensin family." Proceedings of the National Academy of Sciences 117, no. 1 (December 23, 2019): 337–45. http://dx.doi.org/10.1073/pnas.1912941117.
Full textAbstract:
Out of the 14 avian β-defensins identified in theGallus gallusgenome, only 3 are present in the chicken egg, including the egg-specific avian β-defensin 11 (Gga-AvBD11). Given its specific localization and its established antibacterial activity,Gga-AvBD11 appears to play a protective role in embryonic development.Gga-AvBD11 is an atypical double-sized defensin, predicted to possess 2 motifs related to β-defensins and 6 disulfide bridges. The 3-dimensional NMR structure of the purifiedGga-AvBD11 is a compact fold composed of 2 packed β-defensin domains. This fold is the archetype of a structural family, dubbed herein as avian-double-β-defensins (Av-DBD). We speculate thatAvBD11emanated from a monodomain gene ancestor and that similar events might have occurred in arthropods, leading to another structural family of less compact DBDs. We show thatGga-AvBD11 displays antimicrobial activities against gram-positive and gram-negative bacterial pathogens, the avian protozoanEimeria tenella, and avian influenza virus.Gga-AvBD11 also shows cytotoxic and antiinvasive activities, suggesting that it may not only be involved in innate protection of the chicken embryo, but also in the (re)modeling of embryonic tissues. Finally, the contribution of either of the 2Gga-AvBD11 domains to these biological activities was assessed, using chemically synthesized peptides. Our results point to a critical importance of the cationic N-terminal domain in mediating antibacterial, antiparasitic, and antiinvasive activities, with the C-terminal domain potentiating the 2 latter activities. Strikingly, antiviral activity in infected chicken cells, accompanied by marked cytotoxicity, requires the full-length protein.
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Shi, Jishu, Shelly Aono, Wuyuan Lu, Andre J. Ouellette, Lei Wang, Stephen Lenz, and Charles O. Elson. "Regulation of IL-1beta secretion by defensins (100.11)." Journal of Immunology 178, no. 1_Supplement (April 1, 2007): S199. http://dx.doi.org/10.4049/jimmunol.178.supp.100.11.
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Abstract Impaired expression of antimicrobial peptides α defensins and overproduction of proinflammatory cytokine IL-1β have been associated with inflammatory bowel disease (IBD). In this study, we examine the interactions between defensins and IL-1β and the role of defensin-deficiency in the pathogenesis of IBD. It was found that matrix metalloproteinase-7 deficient (MMP-7−/−) mice, which produce procryptdins but not mature cryptdins (α-defensins) in the intestine, were more susceptible to dextran sulfate sodium (DSS)-induced colitis. Furthermore, the baseline and DSS-induced IL-1β production in the intestine are significantly up-regulated in MMP-7−/− mice compared with that in WT mice. To elucidate the molecular mechanism for the increased IL-1β production in defensin-deficiency in vivo, we evaluated the effect of defensins on IL-1β posttranslational processing and release. It was found that α defensins, including human neutrophil defensin HNP-1, human Paneth cell defensin HD-5, and mouse Paneth cell defensins cryptdin-3 and cryptdin-4, can block the release of IL-1β from LPS-activated monocytes. However, TNF α expression and release from LPS-activated monocytes are not affected by defensins. Unlike α defensins, human β defensins and mouse procryptdins do not have any effect on IL-1β processing and release. Thus, α-defensins may play an important role in intestinal homeostasis by controlling the production of IL-1β.
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Brancaccio, Mariarita, Cristina Mennitti, Mariella Calvanese, Alessandro Gentile, Roberta Musto, Giulia Gaudiello, Giulia Scamardella, et al. "Diagnostic and Therapeutic Potential for HNP-1, HBD-1 and HBD-4 in Pregnant Women with COVID-19." International Journal of Molecular Sciences 23, no. 7 (March 22, 2022): 3450. http://dx.doi.org/10.3390/ijms23073450.
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Pregnancy is characterized by significant immunological changes and a cytokine profile, as well as vitamin deficiencies that can cause problems for the correct development of a fetus. Defensins are small antimicrobial peptides that are part of the innate immune system and are involved in several biological activities. Following that, this study aims to compare the levels of various cytokines and to investigate the role of defensins between pregnant women with confirmed COVID-19 infection and pregnant women without any defined risk factor. TNF-α, TGF-β, IL-2 and IL-10, β-defensins, have been evaluated by gene expression in our population. At the same time, by ELISA assay IL-6, IL-8, defensin alpha 1, defensin beta 1 and defensin beta 4 have been measured. The data obtained show that mothers affected by COVID-19 have an increase in pro-inflammatory factors (TNF-α, TGF-β, IL-2, IL-6, IL-8) compared to controls; this increase could generate a sort of “protection of the fetus” from virus attacks. Contemporarily, we have an increase in the anti-inflammatory cytokine IL-10 and an increase in AMPs, which highlights how the mother’s body is responding to the viral attack. These results allow us to hypothesize a mechanism of “trafficking” of antimicrobial peptides from the mother to the fetus that would help the fetus to protect itself from the infection in progress.
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Guyot, Nicolas, Céline Landon, and Philippe Monget. "The Two Domains of the Avian Double-β-Defensin AvBD11 Have Different Ancestors, Common with Potential Monodomain Crocodile and Turtle Defensins." Biology 11, no. 5 (April 30, 2022): 690. http://dx.doi.org/10.3390/biology11050690.
Full textAbstract:
Beta-defensins are an essential group of cysteine-rich host-defence peptides involved in vertebrate innate immunity and are generally monodomain. Among bird defensins, the avian β-defensin 11 (AvBD11) is unique because of its peculiar structure composed of two β-defensin domains. The reasons for the appearance of such ‘polydefensins’ during the evolution of several, but not all branches of vertebrates, still remain an open question. In this study, we aimed at exploring the origin and evolution of the bird AvBD11 using a phylogenetic approach. Although they are homologous, the N- and C-terminal domains of AvBD11 share low protein sequence similarity and possess different cysteine spacing patterns. Interestingly, strong variations in charge properties can be observed on the C-terminal domain depending on bird species but, despite this feature, no positive selection was detected on the AvBD11 gene (neither on site nor on branches). The comparison of AvBD11 protein sequences in different bird species, however, suggests that some amino acid residues may have undergone convergent evolution. The phylogenetic tree of avian defensins revealed that each domain of AvBD11 is distant from ovodefensins (OvoDs) and may have arisen from different ancestral defensins. Strikingly, our phylogenetic analysis demonstrated that each domain of AvBD11 has common ancestors with different putative monodomain β-defensins from crocodiles and turtles and are even more closely related with these reptilian defensins than with their avian paralogs. Our findings support that AvBD11′s domains, which differ in their cysteine spacing and charge distribution, do not result from a recent internal duplication but most likely originate from a fusion of two different ancestral genes or from an ancestral double-defensin arisen before the Testudines-Archosauria split.
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Patil, Amar, Austin L. Hughes, and Guolong Zhang. "Rapid evolution and diversification of mammalian α-defensins as revealed by comparative analysis of rodent and primate genes." Physiological Genomics 20, no. 1 (December 15, 2004): 1–11. http://dx.doi.org/10.1152/physiolgenomics.00150.2004.
Full textAbstract:
Mammalian α-defensins constitute a family of cysteine-rich, cationic antimicrobial peptides produced by phagocytes and intestinal Paneth cells, playing an important role in innate host defense. Following comprehensive computational searches, here we report the discovery of complete repertoires of the α-defensin gene family in the human, chimpanzee, rat, and mouse with new genes identified in each species. The human genome was found to encode a cluster of 10 distinct α-defensin genes and pseudogenes expanding 132 kb continuously on chromosome 8p23. Such α-defensin loci are also conserved in the syntenic chromosomal regions of chimpanzee, rat, and mouse. Phylogenetic analyses showed formation of two distinct clusters with primate α-defensins forming one cluster and rodent enteric α-defensins forming the other cluster. Species-specific clustering of genes is evident in nonprimate species but not in the primates. Phylogenetically distinct subsets of α-defensins also exist in each species, with most subsets containing multiple members. In addition, natural selection appears to have acted to diversify the functionally active mature defensin region but not signal or prosegment sequences. We concluded that mammalian α-defensin genes may have evolved from two separate ancestors originated from β-defensins. The current repertoires of the α-defensin gene family in each species are primarily a result of repeated gene duplication and positive diversifying selection after divergence of mammalian species from each other, except for the primate genes, which were evolved prior to the separation of the primate species. We argue that the presence of multiple, divergent subsets of α-defensins in each species may help animals to better cope with different microbial challenges in the ecological niches which they inhabit.
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Dietrich, Deborah E., Xiangjun Xiao, Deborah V. Dawson, Myriam Bélanger, Hua Xie, Ann Progulske-Fox, and Kim A. Brogden. "Human α- and β-Defensins Bind to Immobilized Adhesins from Porphyromonas gingivalis." Infection and Immunity 76, no. 12 (October 13, 2008): 5714–20. http://dx.doi.org/10.1128/iai.00997-08.
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ABSTRACT Human neutrophil peptide α-defensins (HNPs) and human β-defensins (HBDs) are small well-characterized peptides with broad antimicrobial activities and a diversity of innate immune functions. Although the interactions of defensins with bacteria and their membranes have been well characterized, the interactions of defensins with bacterial adhesins have not. Here we determine if HNPs and HBDs bind to the immobilized adhesins of Porphyromonas gingivalis strain 381, recombinant hemagglutinin B (rHagB) and recombinant fimbrillin A (rFimA), by surface plasmon resonance spectroscopy. Association of HNPs and HBDs with rHagB or rFimA was dose dependent and defensin specific. HBD3, HNP-2, and HNP-1 bound more readily to immobilized rHagB than HBD2 and HBD1 did. HNP-2, HNP-1, and HBD3 bound more readily to immobilized rFimA than HBD1 and HBD2 did. Binding of defensins to adhesins may serve to prevent microbial adherence to tissues, attenuate proinflammatory cytokine responses, and facilitate delivery of bound antigen to antigen-presenting cells with defensin receptors.
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Sang, Yongming, M. Teresa Ortega, Frank Blecha, Om Prakash, and Tonatiuh Melgarejo. "Molecular Cloning and Characterization of Three β-Defensins from Canine Testes." Infection and Immunity 73, no. 5 (May 2005): 2611–20. http://dx.doi.org/10.1128/iai.73.5.2611-2620.2005.
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ABSTRACT Mammalian β-defensins are small cationic peptides possessing broad antimicrobial and physiological activities. Because dogs are particularly resilient to sexually transmitted diseases, it has been proposed that their antimicrobial peptide repertoire might provide insight into novel antimicrobial therapeutics and treatment regimens. To investigate this proposal, we cloned the full-length cDNA of three canine β-defensin isoforms (cBD-1, -2, and -3) from canine testicular tissues. Their predicted peptides share identical N-terminal 65-amino-acid residues, including the β-defensin consensus six-cysteine motif. The two longer isoforms, cBD-2 and -3, possess 4 and 34 additional amino acids, respectively, at the C terminus. To evaluate the antimicrobial activity of cBD, a 34-amino-acid peptide derived from the shared mature peptide region was synthesized. Canine β-defensin displayed broad antimicrobial activity against gram-positive bacteria (Listeria monocytogenes and Staphylococcus aureus; MICs of 6 and 100 μg/ml, respectively), gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, and Neisseria gonorrhoeae; MICs of 20 to 50, 20, and 50 μg/ml, respectively), and yeast (Candida albicans; MIC of 5 to 50 μg/ml) and lower activity against Ureaplasma urealyticum and U. canigenitalium (MIC of 200 μg/ml). Antimicrobial potency was significantly reduced at salt concentrations higher than 140 mM. All three canine β-defensins were highly expressed in testis. In situ hybridization indicated that cBD-1 was expressed primarily in Sertoli cells within the seminiferous tubules. In contrast, cBD-2 was located primarily within Leydig cells. The longest isoform, cBD-3, was detected in Sertoli cells and to a lesser extent in the interstitium. The tissue-specific expression and broad antimicrobial activity suggest that canine β-defensins play an important role in host defense and other physiological functions of the male reproductive system.
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Pohorielova, O., and O. Shevchenko. "Role of β-defensins in immune response in tuberculosis patients." Inter Collegas 7, no. 2 (July 5, 2020): 102–6. http://dx.doi.org/10.35339/ic.7.2.102-106.
Full textAbstract:
ROLE OF Β-DEFENSINS IN IMMUNE RESPONSE IN TUBERCULOSIS PATIENTS
Shevchenko O., Pohorielova O.
Expanding of tuberculosis drug-resistance makes host-directed treatment an important part of tuberculosis treatment. Host-directed treatment is aimed at stimulating the production of antimicrobial peptides by the patient's immune cells. The use of β-defensins is very interesting in this field because of their pronounced bactericidal and bacteriostatic effects, as well as the ability to stimulate the chemotaxis of immune cells. The article presents a review on the immunological properties of the defensin family and the possibility of their use in practice. To complete the review 114 articles from “PubMed” resource were analyzed to perform the study. 34 of them were chosen to review immunomodulatory and antimicrobial action of β-defensins.
The own research results on Human-beta-defensine-1 use as tuberculosis severity marker are also added to the research. To obtain our own research results, 100 TB patients and 20 healthy persons were included in the study. Human-beta-defensin-1 level in serum was investigated in all the patients at the treatment onset and in healthy persons. Mann-Whitney U test (for comparison of 2 independent groups) and Spearman's rank correlation coefficient were used for statistical data processing. It was found that Human-beta-defensin-1 level was significantly higher in TB patients than in healthy persons. A correlation of medium strength (r=+0.53, p<0.05) between Human-beta-defensin-1 and tuberculosis lesion volume was revealed. The data obtained allows to use human β-defensin-1 as a diagnostic marker of tuberculosis.
Key words: tuberculosis, β-defensins, immunity, prognostic marker
Резюме.
РОЛЬ Β-ДЕФЕНЗИНІВ В ІМУННІЙ ВІДПОВІДІ У ХВОРИХ НА ТУБЕРКУЛЬОЗ
Шевченко О.С., Погорєлова О.О.
Розширення лікарської стійкості туберкульозу робить лікування, спрямоване на активацію власних резервів організму-хазяїна, важливою частиною терапії. Таке лікування спрямоване на стимулювання продукції антимікробних пептидів імунними клітинами пацієнта. Використання β-дефензинів в даній області є перспективним через їх виражену бактерицидну і бактеріостатичну дію, а також здатність стимулювати хемотаксис імунних клітин. У статті представлений огляд імунологічних властивостей сімейства дефензинів і можливостей їх використання на практиці. Для створення огляду було проаналізовано 114 статей з ресурсу «PubMed». З них 34 були обрані для вивчення імуномодулюючої і антимікробної дії β-дефензинів.
Результати власного дослідження можливостей використання β-дефензину-1 також були включені в роботу. Для отримання власних результатів у дослідження було включено 100 хворих на туберкульоз і 20 здорових людей. Рівень β-дефензіну-1 в сироватці крові був досліджений у всіх пацієнтів на початку лікування і у здорових людей. U-критерій Манна-Уїтні (для порівняння 2 незалежних груп) і коефіцієнт кореляції застосовувалися для статистичної обробки даних. Було виявлено, що рівень β-дефензину-1 був значно вищим у хворих на туберкульоз, ніж у здорових людей. Виявлено кореляцію середньої сили (r = + 0,53, р <0,05) між рівнем β-дефензину-1 і об’ємом туберкульозного ураження. Отримані дані дозволяють використовувати β-дефензин-1 в якості діагностичного маркеру перебігу туберкульозу.
Ключові слова: туберкульоз, β-дефензини, імунітет, прогностичний маркер
Резюме.
РОЛЬ Β-ДЕФЕНЗИНОВ В ИММУННОМ ОТВЕТЕ У БОЛЬНЫХ ТУБЕРКУЛЕЗОМ
Шевченко О.С., Погорелова О.А.
Расширение лекарственной устойчивости туберкулеза делает лечение, направленное на активацию резервов организма-хозяина, важной частью терапии. Такое лечение направлено на стимулирование производства антимикробных пептидов иммунными клетками пациента. Использование β-дефензинов в данной области является перспективным из-за их выраженного бактерицидного и бактериостатического действия, а также способности стимулировать хемотаксис иммунных клеток. В статье представлен обзор иммунологических свойств семейства дефензинов и возможности их использования на практике. Для создания обзора было проанализировано 114 статей из ресурса «PubMed». 34 из них были выбраны для изучения иммуномодулирующего и антимикробного действия β-дефензинов.
Собственные результаты исследования возможностей использования β-дефензина-1 в качестве маркера тяжести туберкулеза также были включены в работу. Для получения собственных результатов в исследование были включены 100 больных туберкулезом и 20 здоровых людей. Уровень β-дефензина-1 в сыворотке был исследован у всех пациентов в начале лечения и у здоровых людей. U-критерий Манна-Уитни (для сравнения 2 независимых групп) и коэффициент корреляции Спирмена были использованы для статистической обработки данных. Было обнаружено, что уровень β-дефензина-1 был значительно выше у больных туберкулезом, чем у здоровых людей. Выявлена корреляция средней силы (r = + 0,53, р <0,05) между уровнем β-дефензина-1 и туберкулезного поражения. Полученные данные позволяют использовать β-дефензин-1 в качестве диагностического маркера течения туберкулеза.
Ключевые слова: туберкулез, β-дефензины, иммунитет, прогностический маркер
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Christensen-Quick, Aaron, Mark Lafferty, Marco Goicochea, and Alfredo Garzino-Demo. "β-defensins that bind CCR6: Blunting the permissiveness of Th17 cells to HIV infection (P4432)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 206.4. http://dx.doi.org/10.4049/jimmunol.190.supp.206.4.
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Abstract HIV preferentially depletes IL-17-producing, CD4+ “T helper 17” (Th17) cells from the gut during the acute phase of infection. Th17 cells play a key role in mucosal barrier maintenance and protection against opportunistic infections commonly associated with HIV/AIDS. In response to IL-17, epithelial cells of mucosal barriers secrete β-defensins - a family of secreted, cationic peptides with potent broad-range antimicrobial activity against bacteria, fungi, and viruses including HIV. Our laboratory has shown that the expression of human β-defensin 2 (hBD2) is markedly decreased in the oral mucosa of HIV+ subjects, and that β-defensins, in addition to direct antimicrobial activity, upregulate the HIV restriction factor APOBEC3G via the chemokine receptor CCR6, which is expressed on Th17 cells. In order to characterize the effects of HIV infection on the Th17 subset and determine if β-defensins can protect Th17 cells from HIV infection, activated human primary CD4+ T cells are infected and/or treated with β-defensin, then characterized by flow cytometry. Our results show that IL-17A+ cells from peripheral blood are highly permissive to HIV, and are preferentially lost during infection. In addition, our model suggests that Th17-polarizing cytokines enhance HIV infection, and that β-defensins can protect these cells from infection. Our studies of the factors contributing to protection of Th17 cells may yield new therapeutic targets to protect the Th17 compartment.
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Johnson, Gillian P., Andrew T. Lloyd, Cliona O'Farrelly, Kieran G. Meade, and Sean Fair. "Comparative genomic identification and expression profiling of a novel β-defensin gene cluster in the equine reproductive tract." Reproduction, Fertility and Development 28, no. 10 (2016): 1499. http://dx.doi.org/10.1071/rd14345.
Full textAbstract:
β-defensins are small cationic proteins with potent immunoregulatory and antimicrobial activity. The number of genes encoding these peptides varies significantly between and within species but they have not been extensively characterised in the horse. Here, we describe a systematic search of the Equus caballus genome that identified a cluster of novel β-defensin genes on Chromosome 22, which is homologous to a cluster on bovine Chromosome 13. Close genomic matches were found for orthologs of 13 of the bovine genes, which were named equine β-defensins (eBD) 115, eBD116, eBD117, eBD119, eBD120, eBD122a, eBD123, eBD124, eBD125, eBD126, eBD127, eBD129 and eBD132. As expression of the homologous cluster in cattle was limited to the reproductive tract, tissue sections were obtained from the testis, caput, corpus and cauda epididymis and the vas deferens of three stallions and from the ovary, oviduct, uterine horn, uterus, cervix and vagina of three mares. Using a quantitative real-time polymerase chain reaction approach, each of the novel β-defensin genes showed distinct region-specific patterns of expression. Preferential expression in the caput epididymis of these novel defensins in the stallion and in the oviduct in the mare suggests a possible role in immunoprotection of the equine reproductive tract or in fertility.
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Clarke, D. J., and D. J. Campopiano. "Structural and functional studies of defensin-inspired peptides." Biochemical Society Transactions 34, no. 2 (March 20, 2006): 251–56. http://dx.doi.org/10.1042/bst0340251.
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Mammals have evolved complex self-defence mechanisms to protect themselves from infection. This innate immune system comprises a large family of hundreds of peptides and proteins which have potent antibiotic activity at nanomolar concentrations. The defensins are a group of small cationic peptides which contain a high proportion of positively charged and hydrophobic amino acids. Their exact mechanism of antimicrobial action is unclear, but it is thought that the defensins bind to and disrupt the outer cell membrane which ultimately causes lysis and cell death. They are characterized by six conserved cysteine residues which oxidize to form three intramolecular disulphide (S–S) bonds. The human and mouse defensins have been subdivided into classes based on their sequence, site of expression and the S–S bond connectivity of the cysteine residues. α-Defensins are connected by cysteines 1 and 6, 2 and 4, and 3 and 5, whereas β-defensins have a 1–5, 2–4 and 3–6 cysteine S–S connectivity. We present our structural and functional studies of a novel mouse β-defensin-related peptide (Defr1) which contains only five cysteine residues. Synthetic Defr1 was more active than its six-cysteine analogue against a large panel of pathogens. High-resolution MS techniques revealed that Defr1 contains an unusual defensin structure. These studies have guided the design of novel peptides to explore the roles of defensins as antibiotics and as stimulants of the immune response.
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Sakamoto, Noriho, Hiroshi Mukae, Takeshi Fujii, Hiroshi Ishii, Sumako Yoshioka, Tomoyuki Kakugawa, Kanako Sugiyama, et al. "Differential effects of α- and β-defensin on cytokine production by cultured human bronchial epithelial cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 288, no. 3 (March 2005): L508—L513. http://dx.doi.org/10.1152/ajplung.00076.2004.
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Defensins are cysteine-rich cationic antimicrobial peptides that play an important role in innate immunity and are known to contribute to the regulation of host adaptive immunity. In addition to direct antimicrobial activities, it has been recently reported that α-defensins, mainly present in neutrophils in the lung, have a cytotoxic effect and induce IL-8 production from airway epithelial cells. Although β-defensins are expressed in epithelial cells in various tissues, including lung, there are no reports of their effects on cytokine synthesis in airway epithelial cells. The aim of the present study was to determine the effects of both α- and β-defensins on the cytokine production, transcription factor binding activity, and cytotoxicity in primary cultured human bronchial epithelial cells (HBECs). We used human neutrophil peptide-1 (HNP-1; α-defensin) and human β-defensin-2 (HBD-2) to stimulate HBECs. The results showed that treatment of HBECs with HNP-1, but not HBD-2, increased IL-8 and IL-1β mRNA expression in a dose-dependent manner and also enhanced IL-8 protein secretion and NF-κB DNA binding activity. The 24-h treatments with >20 μg/ml of HNP-1 or >50 μg/ml of HBD-2 were cytotoxic to HBECs. These results suggest that α- and β-defensins have different effects on cytokine synthesis by airway epithelial cells, and we speculate that they play different roles in inflammatory lung diseases.
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Yamaguchi, Yasuhiro, Takahide Nagase, Tetsuji Tomita, Kyoko Nakamura, Shigetomo Fukuhara, Tomokazu Amano, Hiroshi Yamamoto, et al. "β-Defensin overexpression induces progressive muscle degeneration in mice." American Journal of Physiology-Cell Physiology 292, no. 6 (June 2007): C2141—C2149. http://dx.doi.org/10.1152/ajpcell.00295.2006.
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Defensins comprise a family of cationic antimicrobial peptides characterized by conserved cysteine residues. They are produced in various organs including skeletal muscle and are identified as key elements in the host defense system as potent effectors. At the same time, defensins have potential roles in the regulation of inflammation and, furthermore, can exert cytotoxic effects on several mammalian cells. Here, we developed transgenic mice overexpressing mouse β-defensin-6 to explore the pathophysiological roles of the defensin family as a novel mediator of inflammatory tissue injury. Unexpectedly, the transgenic mice showed short lifespan, poor growth, and progressive myofiber degeneration with functional muscle impairment, predominant centronucleated myofibers, and elevated serum creatine kinase activity, as seen in human muscular dystrophy. Furthermore, some of the transgenic myofibers showed IκBα accumulation, which would be related to the myofiber apoptosis of limb-girdle muscular dystrophy type 2A. The present findings may unravel a concealed linkage between the innate immune system and the pathophysiology of degenerative diseases.
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Radhakrishnan, Yashwanth, Mario A. Fares, Frank S. French, and Susan H. Hall. "Comparative genomic analysis of a mammalian β-defensin gene cluster." Physiological Genomics 30, no. 3 (August 2007): 213–22. http://dx.doi.org/10.1152/physiolgenomics.00263.2006.
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Comparative genomic analyses have yielded valuable insights into conserved and divergent aspects of gene function, regulation, and evolution. Herein, we describe the characterization of a mouse β-defensin gene cluster locus on chromosome 2F6. In addition, we present the evolutionary analysis of this cluster and its human, rhesus, and rat orthologs. Expression analysis in mouse revealed the occurrence of defensin cluster transcripts in multiple tissues, with the highest abundance in the urogenital tract. Molecular evolutionary analysis suggests that this cluster originated by a series of duplication events, and by positive selection occurring even after the rodent-primate split. In addition, the constraints analysis showed higher positive selection in rodents than in primates, especially distal to the six-cysteine array. Positive selection in the evolution of these defensins may relate not only to the evolving enhancement of ancestral host defense but also to functional innovations in reproduction. The multiplicity of defensins and their preferential overexpression in the urogenital tract indicate that defensins function in the protection and maintenance of fertility.
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Boniotto, Michele, William J. Jordan, Joyce Eskdale, Alessandro Tossi, Nikolinka Antcheva, Sergio Crovella, Nancy D. Connell, and Grant Gallagher. "Human β-Defensin 2 Induces a Vigorous Cytokine Response in Peripheral Blood Mononuclear Cells." Antimicrobial Agents and Chemotherapy 50, no. 4 (April 2006): 1433–41. http://dx.doi.org/10.1128/aac.50.4.1433-1441.2006.
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ABSTRACT β-Defensins are a family of small cationic peptides involved in the innate response to microbial infection. Although their role in microbial killing is well established, the mechanisms through which this occurs remain largely undefined. Here, using protein array technology, we describe a role for human β-defensins in the induction of an inflammatory cytokine response by human peripheral blood mononuclear cells (PBMCs). Human β-defensins 1, 2, and 3 were examined for induction of an array of cytokines and chemokines. Some cytokines, such as interleukin 8 (IL-8) and monocyte chemoattractant protein 1, were up-regulated by all three defensins, while others, such as IL-6 and IL-10, were induced more selectively. It was notable that each defensin induced a unique pattern of cytokines. This report documents, for the first time, an analysis of the composite cytokine response of human PBMCs to β-defensins. The induction or up-regulation of a number of cytokines involved in the adaptive immune response suggests a possible role for these defensins in linking innate and acquired immunity.
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Ryan, Lisa, Jichuan Wu, Kyell Schwartz, Sunghan Yim, and Gill Diamond. "β-Defensins Coordinate In Vivo to Inhibit Bacterial Infections of the Trachea." Vaccines 6, no. 3 (August 28, 2018): 57. http://dx.doi.org/10.3390/vaccines6030057.
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β-defensins are predicted to play an important role in innate immunity against bacterial infections in the airway. We previously observed that a type III-secretion product of Bordetella bronchiseptica inhibits the NF-κB-mediated induction of a β-defensin in airway epithelial cells in vitro. To confirm this in vivo and to examine the relative roles of other β-defensins in the airway, we infected wild-type C57BL/6 mice and mice with a deletion of the mBD-1 gene with B. bronchiseptica wild-type strain, RB50 and its mutant strain lacking the type III-secretion system, WD3. The bacteria were quantified in the trachea and the nasal tissue and mRNA levels of mouse β-defensin-3 (mBD-3) were assessed after 24 h. Infection with the wild-type bacterial strain resulted in lower mBD-3 mRNA levels in the trachea than in mice infected with the type III-deficient strain. Furthermore, we observed an increase in bacterial numbers of RB50 only in the tracheas of mBD-1-deficient mice. Neutrophils were also more abundant on the trachea in RB50 infected WT mice but not in the bronchiolar lavage fluid (BAL), compared with WD3 infected WT and mBD-1−/− mice, indicating that the coordination of β-defensin chemotactic effects may be confined to tracheal epithelial cells (TEC). RB50 decreased the ability of mice to mount an early specific antibody response, seven days after infection in both WT and mBD-1−/− mice but there were no differences in titers between RB50-infected WT and mBD-1−/− mice or between WD3-infected WT and mBD-1−/− mice, indicating mBD-1 was not involved in induction of the humoral immune response to the B. bronchiseptica. Challenge of primary mouse TEC in vitro with RB50 and WD3, along with IL-1β, further corroborated the in vivo studies. The results demonstrate that at least two β-defensins can coordinate early in an infection to limit the growth of bacteria in the trachea.
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Leonardi, Rosalia, Salvatore Crimi, Francesco De Ponte, Carla Loreto, Evaristo Belli, and Giuseppe Musumeci. "β-defensin-3 and β-defensin-4 in synovial fluids from temporomandibular joints with osteoarthrosis." Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 27, no. 2 (March 2015): 263–66. http://dx.doi.org/10.1016/j.ajoms.2014.02.002.
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Wang, Ruiqin, Deying Ma, Lijuan Lin, Caiyuan Zhou, Zongxi Han, Yuhao Shao, Wenyan Liao, and Shengwang Liu. "Identification and characterization of an avian β-defensin orthologue, avian β-defensin 9, from quails." Applied Microbiology and Biotechnology 87, no. 4 (April 16, 2010): 1395–405. http://dx.doi.org/10.1007/s00253-010-2591-6.
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Kisich, Kevin O., Leonid Heifets, Michael Higgins, and Gill Diamond. "Antimycobacterial Agent Based on mRNA Encoding Human β-Defensin 2 Enables Primary Macrophages To Restrict Growth ofMycobacterium tuberculosis." Infection and Immunity 69, no. 4 (April 1, 2001): 2692–99. http://dx.doi.org/10.1128/iai.69.4.2692-2699.2001.
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ABSTRACT Human macrophages are hosts for Mycobacterium tuberculosis, the causative agent of tuberculosis, which killed approximately 1.87 million people in 1997. Human alveolar macrophages do not express α- or β-defensins, broad-spectrum antimicrobial peptides which are expressed in macrophages from other species more resistant to infection withM. tuberculosis. It has been previously reported thatM. tuberculosis is susceptible to killing by defensins, which may explain the difference in resistance. Defensin peptides have been suggested as a possible therapeutic strategy for a variety of infectious diseases, but development has been hampered by difficulties in their large-scale production. Here we report the cellular synthesis of human β-defensin 2 via highly efficient mRNA transfection of human macrophages. This enabled mycobactericidal and mycobacteristatic activity by the macrophages. Although human macrophages are difficult to transfect with plasmid vectors, these studies illustrate that primary macrophages are permissive for mRNA transfection, which enabled expression of a potentially therapeutic protein.
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Contreras, Gabriela, Nessa Wang, Holger Schäfer, and Michael Wink. "Oxidative stress and the presence of bacteria increase gene expression of the antimicrobial peptide aclasin, a fungal CSαβ defensin in Aspergillus clavatus." PeerJ 7 (February 25, 2019): e6290. http://dx.doi.org/10.7717/peerj.6290.
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Background Antimicrobial peptides (AMPs) represent a broad class of naturally occurring antimicrobial compounds. Plants, invertebrates and fungi produce various AMPs as, for example, defensins. Most of these defensins are characterised by the presence of a cysteine-stabilised α-helical and β-sheet (CSαβ) motif. The changes in gene expression of a fungal CSαβ defensin by stress conditions were investigated in Aspergillus clavatus. A. clavatus produces the CSαβ defensin Aclasin, which is encoded by the aclasin gene. Methods Aclasin expression was evaluated in submerged mycelium cultures under heat shock, osmotic stress, oxidative stress and the presence of bacteria by quantitative real-time PCR. Results Aclasin expression increased two fold under oxidative stress conditions and in the presence of viable and heat-killed Bacillus megaterium. Under heat shock and osmotic stress, aclasin expression decreased. Discussion The results suggest that oxidative stress and the presence of bacteria might regulate fungal defensin expression. Moreover, fungi might recognise microorganisms as plants and animals do.
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Sun, Lingling, Catherine M. Finnegan, Tina Kish-Catalone, Robert Blumenthal, Paolo Garzino-Demo, Gian M. La Terra Maggiore, Sid Berrone, et al. "Human β-Defensins Suppress Human Immunodeficiency Virus Infection: Potential Role in Mucosal Protection." Journal of Virology 79, no. 22 (November 15, 2005): 14318–29. http://dx.doi.org/10.1128/jvi.79.22.14318-14329.2005.
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ABSTRACT β-Defensins are small (3 to 5 kDa in size) secreted antimicrobial and antiviral proteins that are components of innate immunity. β-Defensins are secreted by epithelial cells, and they are expressed at high levels in several mucosae, including the mouth, where the concentration of these proteins can reach 100 μg/ml. Because of these properties, we wondered whether they could be part of the defenses that lower oral transmission of human immunodeficiency virus (HIV) compared to other mucosal sites. Our data show that select β-defensins, especially human β-defensin 2 (hBD2) and hBD3, inhibit R5 and X4 HIV infection in a dose-dependent manner at doses that are compatible with or below those measured in the oral cavity. We observed that β-defensin treatment inhibited accumulation of early products of reverse transcription, as detected by PCR. We could not, however, detect any reproducible inhibition of env-mediated fusion, and we did not observe any modulation of HIV coreceptors following treatment with hBD1 and hBD2, in both resting and phytohemagglutinin-activated cells. Our data instead suggest that, besides a direct inactivation of HIV virions, hBD2 inhibits HIV replication in the intracellular environment. Therefore, we speculate that β-defensins mediate a novel antiretroviral mechanism that contributes to prevention of oral HIV transmission in the oral cavity. Immunohistochemical data on hBD2 expression in oral mucosal tissue shows that hBD2 is constitutively expressed, forming a barrier layer across the epithelium in healthy subjects, while in HIV-positive subjects levels of hBD2 expression are dramatically diminished. This may predispose HIV-positive subjects to increased incidence of oral complications associated with HIV infection.
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Landon, Céline, Yanyu Zhu, Mainak Mustafi, Jean-Baptiste Madinier, Dominique Lelièvre, Vincent Aucagne, Agnes F. Delmas, and James C. Weisshaar. "Real-Time Fluorescence Microscopy on Living E. coli Sheds New Light on the Antibacterial Effects of the King Penguin β-Defensin AvBD103b." International Journal of Molecular Sciences 23, no. 4 (February 12, 2022): 2057. http://dx.doi.org/10.3390/ijms23042057.
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(1) Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics. Among AMPs, the disulfide-rich β-defensin AvBD103b, whose antibacterial activities are not inhibited by salts contrary to most other β-defensins, is particularly appealing. Information about the mechanisms of action is mandatory for the development and approval of new drugs. However, data for non-membrane-disruptive AMPs such as β-defensins are scarce, thus they still remain poorly understood. (2) We used single-cell fluorescence imaging to monitor the effects of a β-defensin (namely AvBD103b) in real time, on living E. coli, and at the physiological concentration of salts. (3) We obtained key parameters to dissect the mechanism of action. The cascade of events, inferred from our precise timing of membrane permeabilization effects, associated with the timing of bacterial growth arrest, differs significantly from the other antimicrobial compounds that we previously studied in the same physiological conditions. Moreover, the AvBD103b mechanism does not involve significant stereo-selective interaction with any chiral partner, at any step of the process. (4) The results are consistent with the suggestion that after penetrating the outer membrane and the cytoplasmic membrane, AvBD103b interacts non-specifically with a variety of polyanionic targets, leading indirectly to cell death.
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Olli, Sudar, Ramakrishnan Nagaraj, and Swapna R. Motukupally. "A Hybrid Cationic Peptide Composed of Human β-Defensin-1 and Humanized θ-Defensin Sequences Exhibits Salt-Resistant Antimicrobial Activity." Antimicrobial Agents and Chemotherapy 59, no. 1 (October 27, 2014): 217–25. http://dx.doi.org/10.1128/aac.03901-14.
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ABSTRACTWe have designed a hybrid peptide by combining sequences of human β-defensin-1 (HBD-1) and θ-defensin, in an attempt to generate a molecule that combines the diversity in structure and biological activity of two different peptides to yield a promising therapeutic candidate. HBD-1 was chosen as it is a natural defensin of humans that is constitutively expressed, but its antibacterial activity is considerably impaired by elevated ionic strength. θ-Defensins are expressed in human bone marrow as a pseudogene and are homologous to rhesus monkey circular minidefensins. Retrocyclins are synthetic human θ-defensins. The cyclic nature of the θ-defensin peptides makes them salt resistant, nonhemolytic, and virtually noncytotoxicin vitro. However, a nonhuman circular molecule developed for clinical use would be less viable than a linear molecule. In this study, we have fused the C-terminal region of HBD-1 to the nonapeptide sequence of a synthetic retrocyclin. Cyclization was achieved by joining the terminal ends of the hybrid peptide by a disulfide bridge. The hybrid peptide with or without the disulfide bridge exhibited enhanced antimicrobial activity against both Gram-negative and Gram-positive bacteria as well as against fungi, including clinical bacterial isolates from eye infections. The peptide retained activity in the presence of NaCl and serum and was nonhemolyticin vitro. Thus, the hybrid peptide generated holds potential as a new class of antibiotics.
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Brissette, Catherine A., and Sheila A. Lukehart. "Mechanisms of Decreased Susceptibility to β-Defensins by Treponema denticola." Infection and Immunity 75, no. 5 (February 26, 2007): 2307–15. http://dx.doi.org/10.1128/iai.01718-06.
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ABSTRACT Treponema denticola, a periodontal pathogen, is relatively resistant to human beta-defensins, which are small cationic antimicrobial peptides produced by a number of cells, including the gingival epithelium. Using two independent methods, we previously demonstrated that T. denticola proteases are not responsible for decreased vulnerability to defensins. In this study, we confirmed that the major outer membrane protease, dentilisin, is not responsible for T. denticola insensitivity to defensins and examined several other possible mechanisms, including reduced binding to the bacterial surface and efflux pump activity. It has been suggested that some bacteria mask their surfaces with serum proteins. T. denticola grown in a serum-free medium did not exhibit increased susceptibility to human beta-defensin 2 and 3 (hβD-2 and hβD-3, respectively), suggesting that cloaking of the outer surface with host proteins is not involved in defensin resistance. Nonetheless, we demonstrated that T. denticola binds significantly less hβD-2 and -3 than susceptible organisms bind, suggesting that the unusual outer membrane composition of T. denticola may discourage cationic peptide binding. Efflux pumps have been shown to mediate resistance to antibiotics and cationic peptides in other bacteria, and their role in T. denticola's relative resistance to β-defensins was investigated. Three inhibitors of bacterial ATP-binding cassette (ABC) efflux pumps had no effect on T. denticola's susceptibility to hβD-2 or -3. In contrast, a proton motive force inhibitor, carbonyl cyanide 3-chlorophenylhydrazone, increased the susceptibility of T. denticola to killing by hβD-3, demonstrating a potential role for efflux pumps (other than ABC pumps) in resistance to this peptide. Our data suggest that the combination of decreased defensin binding and efflux of any peptide which enters the cytoplasm may explain T. denticola's relative resistance to human beta-defensins.
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Wei, Hong Tao, Zhong Wen Lv, Xue Mei Han, and Guo Li Zhang. "High Expression and Preliminary Purification of Human β-Defensin-2 Fusion Protein." Advanced Materials Research 781-784 (September 2013): 1076–79. http://dx.doi.org/10.4028/www.scientific.net/amr.781-784.1076.
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This study was undertaken to achieve high expression and preliminary purification of human β-defensin-2 fusion protein to lay a solid foundation for production of human β-defensin-2 using genetic engineering. A prokaryotic expression vector for human β-defensin-2 fusion protein was generated using in vitro gene synthesis before transformation into BL21 (l DE3) plysS TrX-B host bacteria. High expression of TrX-A-HBD-2 fusion protein was induced with IPTG in the bacteria exposed to various expression conditions. The fusion protein then underwent preliminary purification. The protein of interest was released from the genetically engineered bacteria after freezing and thawing. The expression of the target protein accounted for 16.12% of the total bacterial proteins. Fractional precipitation with saturated ammonium sulfate and metal chelate affinity chromatography yielded human β-defensin-2 peptide fusion protein, with a relative purity of 80.53%.Human β-defensin-2 fusion protein could be highly expressed in a soluble form, with a relatively high purity
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Zuo, Mingxiang, Xiaoxia Li, Shuang Liu, Bin Chen, and Du Cheng. "Nuclear-Targeting Delivery of CRISPRa System for Upregulation of β-Defensin against Virus Infection by Dexamethasone and Phenylalanine Dual-Modified Dendrimer." Advances in Polymer Technology 2020 (May 4, 2020): 1–13. http://dx.doi.org/10.1155/2020/6582825.
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The dual-modified dendrimer containing dexamethasone (DET) and phenylalanine (Phe) was prepared to deliver plasmid DNA encoding dCas9 and single-guide RNA (sgRNA) for specific upregulation of β-defensin. DET and Phe moieties synergistically enhanced the transfection efficiency and reduced cytotoxicity of dendrimers. Combination of three sgRNAs targeting β-defensin gene demonstrated higher activation efficacy of β-defensin than any single sgRNA and combinations of any two sgRNAs, showing an efficient inhibition of virus infection and replication. The titer of vesicular stomatitis virus (VSV) in the cells treated with dCas9-sgRNA targeting β-defensin was reduced by about 100-fold compared to that of cells treated with dCas9-scramble sgRNA (dCas9-scr sgRNA). In vivo experiments demonstrated that the DET- and Phe-modified dendrimer effectively delivered plasmid DNA encoding dCas9 protein into the airway epithelium, inducing β-defensin expression. Delivery of the CRISPR activation system by a dendrimer modified with DET and Phe was a promising approach against viral disease.
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De Brito Penna Forte, Lilibeth Ferraz, Sheila Cavalca Cortelli, José Roberto Cortelli, Davi Romeiro Aquino, Maria Valéria Costa De Campos, Karina Cogo, Fernando Oliveira Costa, and Gilson Cesar Nobre Franco. "Psychological stress has no association with salivary levels of β-defensin 2 and β-defensin 3." Journal of Oral Pathology & Medicine 39, no. 10 (August 31, 2010): 765–69. http://dx.doi.org/10.1111/j.1600-0714.2010.00933.x.
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Röhrl, Johann, De Yang, Joost J. Oppenheim, and Thomas Hehlgans. "Identification and Biological Characterization of Mouse β-Defensin 14, the Orthologue of Human β-Defensin 3." Journal of Biological Chemistry 283, no. 9 (December 31, 2007): 5414–19. http://dx.doi.org/10.1074/jbc.m709103200.
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Argimón, Silvia, Saranna Fanning, Jill R. Blankenship, and Aaron P. Mitchell. "Interaction between the Candida albicans High-Osmolarity Glycerol (HOG) Pathway and the Response to Human β-Defensins 2 and 3." Eukaryotic Cell 10, no. 2 (December 3, 2010): 272–75. http://dx.doi.org/10.1128/ec.00133-10.
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ABSTRACT Human β-defensins 2 and 3 are small cationic peptides with antimicrobial activity against the fungal pathogen Candida albicans . We found that hog1 and pbs2 mutants were hypersensitive to treatment with these peptides, pointing to a role of the high-osmolarity glycerol (HOG) pathway in the response to defensin-induced cell injury.