Journal articles: 'HBND2'

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Beadell, Brent A., Andy Chieng, Kevin R. Parducho, Zhipeng Dai, Sam On Ho, Gary Fujii, Yixian Wang, and Edith Porter. "Nano- and Macroscale Imaging of Cholesterol Linoleate and Human Beta Defensin 2-Induced Changes in Pseudomonas aeruginosa Biofilms." Antibiotics 10, no. 11 (October 20, 2021): 1279. http://dx.doi.org/10.3390/antibiotics10111279.

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The biofilm production of Pseudomonas aeruginosa (PA) is central to establishing chronic infection in the airways in cystic fibrosis. Epithelial cells secrete an array of innate immune factors, including antimicrobial proteins and lipids, such as human beta defensin 2 (HBD2) and cholesteryl lineolate (CL), respectively, to combat colonization by pathogens. We have recently shown that HBD2 inhibits biofilm production by PA, possibly linked to interference with the transport of biofilm precursors. Considering that both HBD2 and CL are increased in airway fluids during infection, we hypothesized that CL synergizes with HBD2 in biofilm inhibition. CL was formulated in phospholipid-based liposomes (CL-PL). As measured by atomic force microscopy of single bacteria, CL-PL alone and in combination with HBD2 significantly increased bacterial surface roughness. Additionally, extracellular structures emanated from untreated bacterial cells, but not from cells treated with CL-PL and HBD2 alone and in combination. Crystal violet staining of the biofilm revealed that CL-PL combined with HBD2 effected a significant decrease of biofilm mass and increased the number of larger biofilm particles consistent with altered cohesion of formed biofilms. These data suggest that CL and HBD2 affect PA biofilm formation at the single cell and community-wide level and that the community-wide effects of CL are enhanced by HBD2. This research may inform future novel treatments for recalcitrant infections in the airways of CF patients.

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Xi, Gang, Melissa A. Solum, Christine Wai, Laura A. Maile, Clifford J. Rosen, and David R. Clemmons. "The Heparin-Binding Domains of IGFBP-2 Mediate Its Inhibitory Effect on Preadipocyte Differentiation and Fat Development in Male Mice." Endocrinology 154, no. 11 (November 1, 2013): 4146–57. http://dx.doi.org/10.1210/en.2013-1236.

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IGF-binding protein (IGFBP)-2 overexpression confers resistance to high-fat feeding and inhibits the differentiation of preadipocytes in vitro. However, whether administration of IGFBP-2 can regulate adipogenesis in vivo and the domains that mediate this response have not been defined. IGFBP-2 contains 2 heparin-binding domains (HBD), which are localized in the linker region (HBD1) and C-terminal region (HBD2) of IGFBP-2. To determine the relative importance of these domains, we used synthetic peptides as well as mutagenesis. Both HBD1 and HBD2 peptides inhibited preadipocyte differentiation, but the HBD2 peptide was more effective. Selective substitution of charged residues in the HBD1 or HBD2 regions attenuated the ability of the full-length protein to inhibit cell differentiation, but the HBD2 mutant had the greatest reduction. To determine their activities in vivo, pegylated forms of each peptide were administered to IGFBP-2−/− mice for 12 weeks. Magnetic resonance imaging scanning showed that only the HBD2 peptide significantly reduced (48 ± 9%, P < .05) gain in total fat mass. Both inguinal (32 ± 7%, P < .01) and visceral fat (44 ± 7%, P < .01) were significantly decreased by HBD2 whereas HBD1 reduced only visceral fat accumulation (24 ± 5%, P < .05). The HBD2 peptide was more effective peptide in reducing triglyceride content and serum adiponectin, but only the HBD2 peptide increased serum leptin. These findings demonstrate that the HBD2 domain of IGFBP-2 is the primary region that accounts for its ability to inhibit adipogenesis and that a peptide encompassing this region has activity that is comparable with native IGFBP-2.

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Routsias, John G., Dionysia Marinou, Maria Mavrouli, Athanasios Tsakris, and Vassiliki Pitiriga. "Serum β-Defensin 2, A Novel Biomarker for the Diagnosis of Acute Infections." Diagnostics 13, no. 11 (May 28, 2023): 1885. http://dx.doi.org/10.3390/diagnostics13111885.

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Background: Defensins are natural antimicrobial peptides that the human body secretes to protect itself from an infection. Thus, they are ideal molecules to serve as biomarkers for infection. This study was conducted to evaluate the levels of human β-defensins in patients with inflammation. Methods: CRP, hBD2 and procalcitonin were measured in 423 sera of 114 patients with inflammation and healthy individuals using nephelometry and commercial ELISA assays. Results: Levels of hBD2 in the serum of patients with an infection were markedly elevated compared to those of hBD2 in patients with inflammation of non-infectious etiology (p < 0.0001, t = 10.17) and healthy individuals. ROC analysis demonstrated that hBD2 showed the highest detection performance for infection (AUC 0.897; p < 0.001) followed by PCT (AUC 0.576; p = ns) and CRP (AUC 0.517; p = ns). In addition, analysis of hBD2 and CRP in patients’ sera collected at different time points showed that hBD2 levels could help differentiate inflammation of infectious and non-infectious etiology during the first 5 days of hospitalization, while CRP levels could not. Conclusions: hBD2 has the potential to serve as a diagnostic biomarker for infection. In addition, the levels of hBD2 may reflect the efficacy of antibiotic treatment.

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Hosny, Alaa El-Dien Shawky, Mohammed Abdelhalim Ramadan, Maha Ahmed Shafik, Mahmoud Ahmed Shafeek, and Rania Abdelmonem Khattab. "Expression levels of pro-inflammatory interleukin-8 and certain antimicrobial peptides in concurrent with bacterial conjunctivitis." International Journal of Ophthalmology 14, no. 5 (May 18, 2021): 666–75. http://dx.doi.org/10.18240/ijo.2021.05.05.

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AIM: To detect the quantitative expression levels of the pro-inflammatory interleukin-8 (IL8), antimicrobial peptides human beta defense-2 (HBD2), and human beta defense-3 (HBD3) genes in bacterial conjunctivitis. METHODS: The human conjunctival epithelial cells were obtained using the impression cytology technique from healthy controls and patients. The genes expression levels were determined utilizing a reverse transcription quantitative polymerase chain reaction (RT-qPCR). The contribution of causative agent type, the number of isolates and severity of clinical features, in the increase of genes expression was also determined. RESULTS: The RT-qPCR showed that IL8, HBD2, and HBD3 expression increased in bacterial conjunctivitis as compared to healthy control (P<0.001). In gram-negative bacterial conjunctivitis, HBD2 was highly up-regulated (P<0.001) compared to other types of bacterial conjunctivitis. In mixed bacterial conjunctivitis, a direct correlation between HBD2 up-regulation and HBD3 up-regulation was observed (P<0.05). The severity of clinical features was related to the up-regulation of IL8 and HBD2 (P<0.05). CONCLUSION: IL8, HBD2, and HBD3 are immune-effectors in infectious conjunctivitis. HBD2 is active during different bacterial conjunctivitis but is more released with gram-negative bacteria compared to gram-positive bacteria. HBD3 is an obvious defender in different bacterial conjunctivitis.

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Yin, Lei, and Beverly A. Dale. "Activation of protective responses in oral epithelial cells by Fusobacterium nucleatum and human β-defensin-2." Journal of Medical Microbiology 56, no. 7 (July 1, 2007): 976–87. http://dx.doi.org/10.1099/jmm.0.47198-0.

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Oral epithelia are constantly exposed to non-pathogenic (commensal) bacteria, but generally remain healthy and uninflamed. Fusobacterium nucleatum, an oral commensal bacterium, strongly induces human β-defensin-2 (hBD2), an antimicrobial and immunomodulatory peptide, in gingival epithelial cells (GECs). hBD2 is also expressed in normal oral tissue leading to the hypothesis that oral epithelia are in an activated state with respect to innate immune responses under normal in vivo conditions. In order to test this hypothesis, global gene expression was evaluated in GECs in response to stimulation by an F. nucleatum cell wall (FnCW) preparation and to hBD2 peptide. FnCW treatment altered 829 genes, while hBD2 altered 209 genes (P<0.005, ANOVA). Many induced genes were associated with the gene ontology categories of immune responses and defence responses. Consistent with the hypothesis, similar responses were activated by commensal bacteria and hBD2. These responses included up-regulation of common antimicrobial effectors and chemokines, and down-regulation of proliferation markers. In addition, FnCW up-regulated multiple protease inhibitors, and suppressed NF-κB function and the ubiquitin/proteasome system. These global changes may protect the tissue from inflammatory damage. Both FnCW and hBD2 also up-regulated genes that may enhance the epithelial barrier. The findings suggest that both commensal bacteria and hBD2 activate protective responses of GECs and play an important role in immune modulation in the oral cavity.

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Harris, Peggy, Amber Kerstetter-Fogle, Anthony Sloan, Alankrita Raghavan, Harry Hoffman, Jill Barnholtz-Sloan, Marta Couce, Ge Jin, Aaron Weinberg, and Andrew Sloan. "STEM-20. THE ROLE OF HUMAN BETA DEFENSINS IN THE CLONOGENICITY OF GLIOBLASTOMA MULTIFORME." Neuro-Oncology 23, Supplement_6 (November 2, 2021): vi25. http://dx.doi.org/10.1093/neuonc/noab196.094.

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Abstract INTRODUCTION Glioblastoma (GBM) is the most common primary malignant brain tumor with a median overall survival of 12-15months. GBM aggressiveness and poor response to treatment are often attributed to a small population of stem-like cells referred to as glioma stem cells (GSCs). Human Beta-Defensins (HBDs), a family of small molecules initially thought to function as anti-microbials, have been implicated in various cancers with functions that are cancer type specific, including proinflammatory and immunosuppressive roles. GOAL: This study aimed to elucidate HBDs expression in GSCs and differentiated gioma cells (DGSs). METHODS We identified HBD2 and HBD3 in glioma and GSCs and DGSs by immunofluorescence (IF) and immunohistochemistry (IHC). We also assessed the role HBD2/3 play in GBM oncogenesis by investigating their effects on the self-renewal capacity of GSCs. RESULTS HBD2 and HBD3 are found in both bulk tumor and GSCs by IHC and IF. Expression of HBD2 and HBD3 mRNA levels are elevated in GBM patient tissue in comparison to lower grade gliomas by 16.2 & 1.9 fold (respectively; p < 0.0001). Additionally, transcriptional expression of HBD2 and HBD3 are increased by 0.68 and 1.15 fold respectively in GSCs versus autologous DGCs (p < 0.05; p< 0.005 respectively), suggesting a role for HBD 2/3 in oncogenesis. Interestingly however, HBD2 and HBD3 pretreatment of GSC cell lines showed decreased self-renewal capacity by 34.2 and 66.4% (p < 0.001), determined by the reduced number of large neurospheres ( >250mm). CONCLUSIONS Our results demonstrate the presence of HBD2/3 in GBM samples by IHC and IF with increased HBD2/3 mRNA expression in GBM samples. Interestingly DGCs contain less HBD2/3 than their GCS counterparts, and clonogenicity assays demonstrate a decrease in oncogenesis, suggesting that HBD’s role in proliferation and clonogenicity of DGCs and GSCs may be context dependent, leading to additional questions and future studies.

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Ouhara, Kazuhisa, Hitoshi Komatsuzawa, Hideki Shiba, Yushi Uchida, Toshihisa Kawai, Koji Sayama, Koji Hashimoto, Martin A. Taubman, Hidemi Kurihara, and Motoyuki Sugai. "Actinobacillus actinomycetemcomitans Outer Membrane Protein 100 Triggers Innate Immunity and Production of β-Defensin and the 18-Kilodalton Cationic Antimicrobial Protein through the Fibronectin-Integrin Pathway in Human Gingival Epithelial Cells." Infection and Immunity 74, no. 9 (September 2006): 5211–20. http://dx.doi.org/10.1128/iai.00056-06.

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ABSTRACT Antimicrobial peptides, human β-defensin (hBD), and the 18-kDa cationic antimicrobial protein (CAP18) are components of innate immunity. These peptides have antimicrobial activity against bacteria, fungi, and viruses. Actinobacillus actinomycetemcomitans is a gram-negative facultative anaerobe implicated in the initiation of periodontitis. The innate immunity peptides have antibacterial activity against A. actinomycetemcomitans. We investigated the molecular mechanism of human gingival epithelial cells (HGEC) responding to exposure to A. actinomycetemcomitans. HGEC constitutively express hBD1 and inducibly express hBD2, hBD3, and CAP18 on exposure to A. actinomycetemcomitans. The level of expression varies among clinical isolates. In the signaling pathway for hBD2 induction by the bacterial contact, we demonstrate that the mitogen-activated protein (MAP) kinase and not the NF-κB transcription factor pathway is used. We found the outer membrane protein 100 (Omp100; identified by molecular mass) is the component inducing the hBD2 response. Omp100 binds to fibronectin, an extracellular matrix inducing hBD2 via the MAP kinase pathway. Anti-integrin α5β1, antifibronectin, genistein, and PP2 suppress the Omp100-induced expression of hBD2, suggesting that Src kinase is involved through integrin α5β1. The inflammatory cytokines, tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-8, produced by HGEC on contact with A. actinomycetemcomitans also stimulate expression of hBD2. Further, neutralizing antibody against TNF-α or IL-8 partially inhibits the induction of hBD2 on bacterial contact. Therefore, we found that the induction of the antimicrobial peptides is mediated by a direct response principally through an Omp100-fibronectin interaction, and using secondary stimulation by inflammatory cytokines induced by the bacterial exposure.

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Antcheva, Nikolinka, Michele Boniotto, Igor Zelezetsky, Sabrina Pacor, Maria Vittoria Verga Falzacappa, Sergio Crovella, and Alessandro Tossi. "Effects of Positively Selected Sequence Variations in Human and Macaca fascicularis β-Defensins 2 on Antimicrobial Activity." Antimicrobial Agents and Chemotherapy 48, no. 2 (February 2004): 685–88. http://dx.doi.org/10.1128/aac.48.2.685-688.2004.

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ABSTRACT The evolution of orthologous genes coding for β-defensin 2 (BD2) in primates has been subject to positive selection during the divergence of the platyrrhines from the catarrhines and of the Cercopithecidae from the Hylobatidae, great apes, and humans. Three peptides have been selected for a functional analysis of the effects of sequence variations on the direct antimicrobial activity: human BD2 (hBD2), Macaca fascicularis BD2 (mfaBD2), and a variant of the human peptide lacking Asp4, (−D)hBD2, which is characteristic only of the human/great ape peptides. hBD2 and mfaBD2 showed a significant difference in specificity, the former being more active towards Escherichia coli and the later towards Staphylococcus aureus and Candida albicans. Asp4 in the human peptide appears to be important, as (−D)hBD2 was less structured and had a markedly lower antimicrobial activity. The evolution of β-defensin 2 in primates may thus have been driven, at least in part, by different environmental pressures so as to modulate antimicrobial activity.

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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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Zaynullina, O. N., D. V. Pechkurov, Z. R. Khismatullina, and K. R. Mirkhaidarova. "Human beta-defensin 2, secretory immunoglobulin A, and lysozyme in different specimens of children with atopic dermatitis." Voprosy praktičeskoj pediatrii 16, no. 6 (2021): 45–51. http://dx.doi.org/10.20953/1817-7646-2021-6-45-51.

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Objective. To evaluate the levels of human beta-defensin 2 (HBD2), secretory immunoglobulin A (sIgA), and lysozyme in various biological specimens from children with atopic dermatitis and to assess their correlation with the severity of clinical manifestations. Patients and methods. This study included 96 children with atopic dermatitis and 31 healthy controls. We measured serum HBD2, salivary and fecal sIgA, and salivary and fecal lysozyme using special ELISA Kits (CUSABIO, Korea). Results. In children with atopic dermatitis, median levels of serum HBD2 (544 pg/mL [range: 288; 719]), salivary sIgA (120 ng/mL [range: 89.5; 214.5]), fecal sIgA (244 ng/mL [range: 196; 367]), and salivary lysozyme (0.59 ng/ml [range: 0.25; 1.82]) were significantly lower than those in controls (1136 pg/mL [range: 741; 1511], 313 ng/mL [range: 208.5; 356.0], 1582 ng/mL [range: 855; 1710], and 1.65 ng/mL [range: 0.18; 2.58], respectively). We found a strong negative correlation between the SCORAD index and serum HBD2 level (ρ = -0.71, p = 0.005), as well as fecal sIgA (ρ = -0.74, p = 0.032). There was also a negative correlation between the SCORAD index and salivary sIgA (ρ = -0.64, p = 0.032) and salivary lysozyme (ρ = -0.58, p = 0.046). Conclusion. Our findings support the hypothesis that children with atopic dermatitis have reduced production of humoral factors of natural resistance and immunity. The level of HBD2, sIgA, and lysozyme can serve as a biomarker of disease severity. Key words: atopic dermatitis, children, defensins, lysozyme, secretory immunoglobulin A

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LEITCH, G. J., and C. CEBALLOS. "A role for antimicrobial peptides in intestinal microsporidiosis." Parasitology 136, no. 2 (December 12, 2008): 175–81. http://dx.doi.org/10.1017/s0031182008005313.

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SUMMARYClinical isolates from 3 microsporidia species,Encephalitozoon intestinalisandEncephalitozoon hellem, and the insect parasiteAnncaliia(Brachiola, Nosema) algerae, were used in spore germination and enterocyte-like (C2Bbe1) cell infection assays to determine the effect of a panel of antimicrobial peptides. Spores were incubated with lactoferrin (Lf), lysozyme (Lz), and human beta defensin 2 (HBD2), human alpha defensin 5 (HD5), and human alpha defensin 1 (HNP1), alone and in combination with Lz, prior to germination. Of theEncephalitozoonspecies onlyE. hellemspore germination was inhibited by HNP1, whileA. algeraespore germination was inhibited by Lf, HBD2, HD5 and HNP1, although HBD2 and HD5 inhibition required the presence of Lz. The effects of HBD2 and HD5 on microsporidia enterocyte infection paralleled their effects on spore germination. Lysozyme alone only inhibited infection withA. algerae, while Lf inhibited infection byE. intestinalisandA. algerae. HNP1 significantly reduced enterocyte infection by all 3 parasite species and a combination of Lf, Lz and HNP1 caused a further reduced infection withA. algerae. These data suggest that intestinal antimicrobial peptides contribute to the defence of the intestine against infection by luminal microsporidia spores and may partially determine which parasite species infects the intestine.

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Mansour, Bassel, Ádám Monyók, Márió Gajdács, Balázs Stercz, Nóra Makra, Kinga Pénzes, István Vadnay, Dóra Szabó, and Eszter Ostorházi. "Bladder Tissue Microbiome Composition in Patients of Bladder Cancer or Benign Prostatic Hyperplasia and Related Human Beta Defensin Levels." Biomedicines 10, no. 7 (July 21, 2022): 1758. http://dx.doi.org/10.3390/biomedicines10071758.

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Balance between the microbiome associated with bladder mucosa and human beta defensin (HBD) levels in urine is a dynamic, sensitive and host-specific relationship. HBD1—possessing both antitumor and antibacterial activity—is produced constitutively, while the inducible production of antibacterial HBD2 and HBD3 is affected by bacteria. Elevated levels of HBD2 were shown to cause treatment failure in anticancer immunotherapy. Our aim was to assess the relationship between microbiome composition characteristic of tumor tissue, defensin expression and HBD levels measured in urine. Tissue samples for analyses were removed during transurethral resection from 55 bladder carcinoma and 12 prostatic hyperplasia patients. Microbiome analyses were carried out with 16S rRNS sequencing. Levels of HBD mRNA expression were measured with qPCR from the same samples, and urinary amounts of HBD1, 2 and 3 were detected with ELISA in these patients, in addition to 34 healthy volunteers. Mann–Whitney U test, Wilcoxon rank sum test (alpha diversity) and PERMANOVA analysis (beta diversity) were performed. Defensin-levels expressed in the tumor did not clearly determine the amount of defensin measurable in the urine. The antibacterial and antitumor defensin (HBD1) showed decreased levels in cancer patients, while others (HBD2 and 3) were considerably increased. Abundance of Staphylococcus, Corynebacterium and Oxyphotobacteria genera was significantly higher, the abundance of Faecalibacterium and Bacteroides genera were significantly lower in tumor samples compared to non-tumor samples. Bacteroides, Parabacteroides and Faecalibacterium abundance gradually decreased with the combined increase in HBD2 and HBD3. Higher Corynebacterium and Staphylococcus abundances were measured together with higher HBD2 and HBD3 urinary levels. Among other factors, defensins and microorganisms also affect the development, progression and treatment options for bladder cancer. To enhance the success of immunotherapies and to develop adjuvant antitumor therapies, it is important to gain insight into the interactions between defensins and the tumor-associated microbiome.

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Moranta, David, Verónica Regueiro, Catalina March, Enrique Llobet, Javier Margareto, Eider Larrate, Junkal Garmendia, and José A. Bengoechea. "Klebsiella pneumoniae Capsule Polysaccharide Impedes the Expression of β-Defensins by Airway Epithelial Cells." Infection and Immunity 78, no. 3 (December 14, 2009): 1135–46. http://dx.doi.org/10.1128/iai.00940-09.

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ABSTRACT Human β-defensins (hBDs) contribute to the protection of the respiratory tract against pathogens. It is reasonable to postulate that pathogens have developed countermeasures to resist them. Klebsiella pneumoniae capsule polysaccharide (CPS), but not the lipopolysaccharide O antigen, mediated resistance against hBD1 and hBD2. hBD3 was the most potent hBD against Klebsiella. We investigated the possibility that as a strategy for survival in the lung, K. pneumoniae may not activate the expression of hBDs. Infection of A549 and normal human bronchial cells with 52145-Δwca K2, a CPS mutant, increased the expression of hBD2 and hBD3. Neither the wild type nor the lipopolysaccharide O antigen mutant increased the expression of hBDs. In vivo, 52145-Δwca K2 induced higher levels of mBD4 and mBD14, possible mouse orthologues of hBD2 and hBD3, respectively, than the wild type. 52145-Δwca K2-dependent upregulation of hBD2 occurred via NF-κB and mitogen-activated protein kinases (MAPKs) p44/42, Jun N-terminal protein kinase (JNK)-dependent pathways. The increase in hBD3 expression was dependent on the MAPK JNK. 52145-Δwca K2 engaged Toll-like receptors 2 and 4 (TLR2 and TLR4) to activate hBD2, whereas hBD3 expression was dependent on NOD1. K. pneumoniae induced the expression of CYLD and MKP-1, which act as negative regulators for 52145-Δwca K2-induced expression of hBDs. Bacterial engagement of pattern recognition receptors induced CYLD and MKP-1, which may initiate the attenuation of proinflammatory pathways. The results of this study indicate that K. pneumoniae CPS not only protects the pathogen from the bactericidal action of defensins but also impedes their expression. These features of K. pneumoniae CPS may facilitate pathogen survival in the hostile environment of the lung.

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Rue, Cary A., and Patrick Ryan. "Characterization of pseudorabies virus glycoprotein C attachment to heparan sulfate proteoglycans." Journal of General Virology 83, no. 2 (February 1, 2002): 301–9. http://dx.doi.org/10.1099/0022-1317-83-2-301.

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Pseudorabies virus first attaches to cells through an interaction between the envelope glycoprotein C (gC) and the cell surface heparan sulfate (HS) that is linked to proteoglycans (HSPGs). The HS-binding domain of gC is composed of three discrete heparin-binding domains (HBDs), designated HBD1, -2 and -3 for their proximity to the amino terminus of gC. Each HBD can independently mediate virus attachment to HS, yet each also exhibits a distinct binding preference for differentially sulfated derivatives of heparin. To demonstrate this, affinity columns composed of wild-type gC or mutant gC retaining a single HBD to capture several HSPGs from cultured pig and bovine kidney cells were used. The wild-type gC column bound all of the HSPGs well and, overall, bound more than 90% of the total sample applied to the column. Columns composed of either HBD2 or -3 bound intermediate amounts (40%) of the total sample applied, while the HBD1 column bound low amounts of HSPGs. HBD2 and -3 columns did not uniformly bind all of the HSPGs from bovine kidney cells, but the same HSPGs were bound with equal efficiency on each column. Thus, despite their different preferences for sulfation patterns on HS side-chains, HBD2 and -3 appear to bind the same proteoglycan cores. These results established a hierarchy of HBD2=HBD3>HBD1 in importance for HSPG binding. These in vitro-binding results correlated with the attachment phenotype of virus strains expressing gC with a single HBD in their envelopes.

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Barrera, Jose, Sanchez Tortolero, Adriana Rivas, Carmen Flores, and Emanuele Gonzales. "Increased expression and levels of human β defensins (hBD2 and hBD4) in adults with dental caries." Journal of Health Sciences 3, no. 2 (September 15, 2013): 88–97. http://dx.doi.org/10.17532/jhsci.2013.70.

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Introduction: Defensins are small anti-microbial peptides produced by epithelial cells. These peptides have a broad range of actions against microorganisms, including Gram-positive and Gram-negative bacteria.Human defensins are classifi ed into two subfamilies, the α-, and β- defensins, which differ in their distribution of disulphide bonds between the six conserved cysteine residues. Defensins are found in salivaand others compartments of the body. Human β defensins 2 (hBD2), beta defensins 4 (hBD4) and alpha defensins 4 (hNP4) in saliva may contributes to vulnerability or resistance to caries. This study aimed to determine a possible correlation between caries and levels of defensins measuring the expression in gingival tissue and concentrations in saliva samples.Methods: Oral examinations were performed on 100 adults of both genders (18-30 years old), and unstimulated whole saliva was collected for immunoassays of the three peptides and for the salivary pH, buffercapacity, protein, and peroxidase activity. mRNA levels of defensins in gingival sample were assessed by semi-quantitative RT-PCR technique.Results: The median salivary levels of hBD2 and hBD4 were 1.88 μg/ml and 0.86 μg/ml respectively for the caries-free group (n=44) and 7.26 μ/ml (hBD2) and 4.25 μg/ml (hBD4) for all subjects with evidenceof caries (n=56). There was no difference in the levels of hNP4, salivary pH, and proteins between groups, however the peroxidase activity and buffer capacity (interval 6.0-5.0) were reduced in caries group. Transcriptional levels of hBD2 and hBD4 did correlate with caries experience, the mRNA expression of hBD2 and hBD4 were signifi cantly higher in patients with caries than in patients with no-caries (p < 0.01).Conclusion: We conclude that high salivary levels and expression of beta defensins, low peroxidase activity and buffer capacity may represent a biological response of oral tissue to caries. Our observation couldlead to new ways to prevent caries and a new tool for caries risk assessment.

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Zarina, Kaiva Zile, and Mara Pilmane. "Characterization of Angiogenic, Matrix Remodeling, and Antimicrobial Factors in Preterm and Full-Term Human Umbilical Cords." Journal of Developmental Biology 12, no. 2 (May 1, 2024): 13. http://dx.doi.org/10.3390/jdb12020013.

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Background: Little is known about morphogenetic changes in the umbilical cord during the maturation process. Extracellular matrix remodeling, angiogenesis, progenitor activity, and immunomodulation are represented by specific markers; therefore, the aim of this study was to determine the expression of matrix metalloproteinase-2 (MMP2), tissue inhibitor of metalloproteinases-2 (TIMP2), CD34, vascular endothelial growth factor (VEGF), and human β-defensin 2 (HBD2) in preterm and full-term human umbilical cord tissue. Methods: Samples of umbilical cord tissue were obtained from 17 patients and divided into two groups: very preterm and moderate preterm birth umbilical cords; late preterm birth and full-term birth umbilical cords. Routine histology examination was conducted. Marker-positive cells were detected using the immunohistochemistry method. The number of positive structures was counted semi-quantitatively using microscopy. Statistical analysis was carried out using the SPSS Statistics 29 program. Results: Extraembryonic mesenchyme cells are the most active cell producers, expressing MMP2, TIMP2, VEGF, and HBD2 at notable levels in preterm and full-term umbilical cord tissue. Statistically significant differences in the expression of CD34, MMP2, and TIMP2 between the two patient groups were found. The expression of VEGF was similar in both patient groups, with the highest number of VEGF-positive cells seen in the extraembryonic mesenchyme. The expression of HBD2 was the highest in the extraembryonic mesenchyme and the amniotic epithelium, where mostly moderate numbers of HBD2-positive cells were detected. Conclusions: Extracellular matrix remodeling in preterm and term umbilical cords is strongly regulated, and tissue factors MMP2 and TIMP2 take part in this process. The expression of VEGF is not affected by the umbilical cord’s age; however, individual patient factors can affect the production of VEGF. Numerous CD34-positive cells in the endothelium of the umbilical arteries suggest a significant role of progenitor cells in very preterm and moderate preterm birth umbilical cords. Antimicrobial activity provided by HBD2 is essential and constant in preterm and full-term umbilical cords.

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Fischer, Natalie, Emmanuel Sechet, Robin Friedman, Aurélien Amiot, Iradj Sobhani, Giulia Nigro, Philippe J. Sansonetti, and Brice Sperandio. "Histone deacetylase inhibition enhances antimicrobial peptide but not inflammatory cytokine expression upon bacterial challenge." Proceedings of the National Academy of Sciences 113, no. 21 (May 9, 2016): E2993—E3001. http://dx.doi.org/10.1073/pnas.1605997113.

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Antimicrobial peptides (AMP) are defense effectors of the innate immunity playing a crucial role in the intestinal homeostasis with commensals and protection against pathogens. Herein we aimed to investigate AMP gene regulation by deciphering specific characteristics allowing their enhanced expression among innate immune genes, particularly those encoding proinflammatory mediators. Our emphasis was on epigenetic regulation of the gene encoding the AMP β-defensin 2 (HBD2), taken as a model of possibly specific induction, upon challenge with a commensal bacterium, compared with the proinflammatory cytokine IL-8. Using an in vitro model of colonic epithelial cells challenged with Escherichia coli K12, we showed that inhibition of histone deacetylases (HDAC) by trichostatin A dramatically enhanced induction of HBD2 expression, without affecting expression of IL-8. This mechanism was supported by an increased phosphorylation of histone H3 on serine S10, preferentially at the HBD2 promoter. This process occurred through activation of the IκB kinase complex, which also led to activation of NF-κB. Moreover, we demonstrated that NF-κB was modified by acetylation upon HDAC inhibition, partly by the histone acetyltransferase p300, and that both NF-κB and p300 supported enhanced induction of HBD2 expression. Furthermore, we identified additional genes belonging to antimicrobial defense and epithelial restitution pathways that showed a similar pattern of epigenetic control. Finally, we confirmed our finding in human colonic primary cells using an ex vivo organoid model. This work opens the way to use epigenetic pharmacology to achieve induction of epithelial antimicrobial defenses, while limiting the deleterious risk of an inflammatory response.

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Midorikawa, Kazushige, Kazuhisa Ouhara, Hitoshi Komatsuzawa, Toshihisa Kawai, Sakuo Yamada, Tamaki Fujiwara, Kenshi Yamazaki, et al. "Staphylococcus aureus Susceptibility to Innate Antimicrobial Peptides, β-Defensins and CAP18, Expressed by Human Keratinocytes." Infection and Immunity 71, no. 7 (July 2003): 3730–39. http://dx.doi.org/10.1128/iai.71.7.3730-3739.2003.

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ABSTRACT The antimicrobial peptides human β-defensin-1 (hBD1), hBD2, hBD3, and CAP18 expressed by keratinocytes have been implicated in mediation of the innate defense against bacterial infection. To gain insight into Staphylococcus aureus infection, the susceptibility of S. aureus, including methicillin-resistant S. aureus (MRSA), to these antimicrobial peptides was examined. Based on quantitative PCR, expression of hBD2 mRNA by human keratinocytes was significantly induced by contact with S. aureus, and expression of hBD3 and CAP18 mRNA was slightly induced, while hBD1 mRNA was constitutively expressed irrespective of the presence of S. aureus. Ten clinical S. aureus isolates, including five MRSA isolates, induced various levels of expression of hBD2, hBD3, and CAP18 mRNA by human kertinocytes. The activities of hBD3 and CAP18 against S. aureus were found to be greater than those of hBD1 and hBD2. A total of 44 S. aureus clinical isolates, including 22 MRSA strains, were tested for susceptibility to hBD3 and CAP18. Twelve (55%) and 13 (59%) of the MRSA strains exhibited more than 20% survival in the presence of hBD3 (1 μg/ml) and CAP18 (0.5 μg/ml), respectively. However, only three (13%) and two (9%) of the methicillin-sensitive S. aureus isolates exhibited more than 20% survival with hBD3 and CAP18, respectively, suggesting that MRSA is more resistant to these peptides. A synergistic antimicrobial effect between suboptimal doses of methicillin and either hBD3 or CAP18 was observed with 10 MRSA strains. Furthermore, of several genes associated with methicillin resistance, inactivation of the fmtC gene in MRSA strain COL increased susceptibility to the antimicrobial effect mediated by hBD3 or CAP18.

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Coello, Daniel, Jeffery D. Knott, and Edith Porter. "In vitro model for assessing the effect of T helper cell cytokines on the barrier function of alveolar type II epithelial cells." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 67.20. http://dx.doi.org/10.4049/jimmunol.202.supp.67.20.

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Abstract There are still diseases of global burden for which satisfactory vaccines are unavailable, e.g. tuberculosis. Vaccines against intracellular microbes has relied on the activation of the adaptive T cell response. Our laboratory is interested in investigating whether the innate epithelial host defense could be integrated in a novel approach. In response to airborne pathogens, airway epithelia release antimicrobial peptides like human beta defensin-2 and -3 (HBD2/3), antimicrobial lipids, and chemokines, like IL-8, to attract other immune cells including T helper cells that are integral to the adaptive immune response. We hypothesize that T cell derived cytokines augment the antimicrobial function of airway epithelia and we have developed an in vitro model to generate pilot data. A549 cells, alveolar type II epithelial cells, were grown in air-liquid interface and stimulated with TNF-α & IFN-γ and IL-17 & IL-22, at 5 ng/mL each, for 24 h. IL-8 and HBD2/3 gene expression was quantified by RT-PCR and secretion of antimicrobial peptides was assessed by AU-PAGE and Western blot probing for HBD2/3. Lipid production was assessed with Bodipy and the physical barrier integrity with Phalloidin. IL-8 gene expression was 9-fold elevated when cells were stimulated with TNF-α & IFN-γ. Secretions from stimulated cells appeared to contain more cationic peptides that were not reactive with HBD2/3 polyclonal antibodies. Cellular Bodipy fluorescence was pronounced after IL-17 & IL22 stimulation. Phalloidin staining was consistent with tight junction formation in all samples. This data provides evidence that T helper cells may directly augment epithelial barrier function supporting a novel vaccine design that integrates the epithelial cell response.

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Subramanian, Hariharan, Kshitij Gupta, Donguk Lee, Arzu Bayir, Harry Ahn, and Hydar Ali. "β-defensins activate human mast cells via Mas-related Gene-X2: cross-regulation by LPS (P4179)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 112.23. http://dx.doi.org/10.4049/jimmunol.190.supp.112.23.

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Abstract Human β-defensins (hBDs) stimulate degranulation in rat peritoneal mast cells and cause increased vascular permeability in wild-type but not mast cell-deficient rats. Here, we sought to determine if hBDs activate murine and human mast cells and to delineate the mechanisms of their regulation. hBD2 and hBD3 did not induce degranulation in murine peritoneal or bone marrow-derived mast cells in vitro and had no effect on vascular permeability in vivo. By contrast, they induced sustained Ca2+ mobilization and substantial degranulation in human mast cells with hBD3 being more potent. While human mast cells endogenously express G protein coupled receptor (GPCR); Mas-related gene X2 (MrgX2), murine mast cells and rat basophilic leukemia, RBL-2H3 cells do not. Silencing the expression of MrgX2 in human mast cells inhibited hBD2/3-induced degranulation and ectopic expression of MrgX2 in RBL-2H3 cells restored these responses. Interestingly, lipopolysaccharide (LPS) inhibited hBD3 but not hBD2-induced Ca2+ mobilization and degranulation. Thus, hBDs activate human mast cells via MrgX2 and that the resistance of murine mast cells likely reflects the absence of this GPCR. Furthermore, the ability of LPS to inhibit hBD3/MrgX2-mediated mast cell activation provides a novel complexity of the role of mast cells in host defense and inflammation.

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Jung, Sascha, Justyna Mysliwy, Björn Spudy, Inken Lorenzen, Karina Reiss, Christoph Gelhaus, Rainer Podschun, Matthias Leippe, and Joachim Grötzinger. "Human β-Defensin 2 and β-Defensin 3 Chimeric Peptides Reveal the Structural Basis of the Pathogen Specificity of Their Parent Molecules." Antimicrobial Agents and Chemotherapy 55, no. 3 (December 28, 2010): 954–60. http://dx.doi.org/10.1128/aac.00872-10.

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ABSTRACTDespite partial sequence identity and structural similarity, human β-defensin 3 (HBD3) killsStaphylococcus aureuswith a 4- to 8-fold higher efficiency than human β-defensin 2 (HBD2), whereas the activities againstEscherichia coliare identical. The design and characterization of HBD2/HBD3 chimeric peptides revealed that distinct molecular regions are responsible for their divergent killing properties. Two of the chimeras killed bothE. coliandS. aureuswith an even higher efficacy than the wild-type molecules. Moreover, one of these two chimeras maintained its high killing activities in the presence of physiologic salt concentrations. Due to the broad spectrum of their antimicrobial activities against many human multidrug-resistant pathogens, these two designer peptides of human origin represent promising templates for a new class of antibiotics.

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PARK, JU YOUN, Jae-Ho Chang, Myong-Jo Kim, and Soo-Ki Kim. "Urushiol regulates the expression of TLR2, HBD and TSLP via NF-κB pathway in Staphylococcus aureus-treated HaCaT cells (134.50)." Journal of Immunology 182, no. 1_Supplement (April 1, 2009): 134.50. http://dx.doi.org/10.4049/jimmunol.182.supp.134.50.

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Abstract TLR2, HBDs(beta-defensins) and TSLP(thymic stromal lymphopoietin) expressed from keratinocytes play key roles in controlling the progression of atopic dermatitis. These molecules might account for the accelerated colonization with S. aureus into eczematous skin barrier. In the course of screening natural substance in regulating TLR2, HBD and TSLP expression by using the inflamed keratinocytes, we found urushiol, major active ingredient of Rhus verniciflua Stokes which has been used as barrier protective in traditional medicine. The aim of this study was to clarify how urushiol regulates innate immune molecules, focused on TLR2, HBD and TSLP, in our in vitro infectious keratinocyte model, S. aureus-treated HaCaT cells. To the end, the expression of TLRs, cytokines and chemokines were assessed by by siRNA, RT-PCR, ELISA and Western blots. We found that urushiol treatment on HaCaT cells induced the expression of TLR2 and HBD2 but not that of TNF-α and TSLP. In S. aureus-treated HaCaT cells, urushiol pretreatment enhanced the expression of TLR2 and HBD2, whereas TNF-α and TSLP expression were in decrement. Further to explore the mechanism, inhibition of NF-κB decreased the expression of TLR2, HBD2 and TSLP, albeit increased TNF-α release. Cumulatively, our data indicate that urushiol regulates the expression of TLR2, HBD and TSLP via NF-κB pathway in S. aureus-treated HaCaT cells.

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Filipe Rosa, Louisa, Andreas Rings, Iris Stolzer, Louis Koeninger, Jan Wehkamp, Julia Beisner, Claudia Günther, Peter Nordkild, Benjamin A. H. Jensen, and Stephan C. Bischoff. "Human α-Defensin 51–9 and Human β-Defensin 2 Improve Metabolic Parameters and Gut Barrier Function in Mice Fed a Western-Style Diet." International Journal of Molecular Sciences 24, no. 18 (September 9, 2023): 13878. http://dx.doi.org/10.3390/ijms241813878.

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Obesity and metabolic comorbidities are associated with gut permeability. While high-fructose and Western-style diet (WSD) disrupt intestinal barrier function, oral administration of human α-defensin 5 (HD5) and β-defensin 2 (hBD2) is believed to improve intestinal integrity and metabolic disorders. Eighty-four male C57BL/6J mice were fed a WSD or a control diet (CD) ± fructose (F) for 18 weeks. In week 13, mice were randomly divided into three intervention groups, receiving defensin fragment HD51–9, full-length hBD2, or bovine serum albumin (BSA)-control for six weeks. Subsequently, parameters of hepatic steatosis, glucose metabolism, and gut barrier function were assessed. WSDF increased body weight and hepatic steatosis (p < 0.01) compared to CD-fed mice, whereas peptide intervention decreased liver fat (p < 0.05) and number of hepatic lipid droplets (p < 0.01) compared to BSA-control. In addition, both peptides attenuated glucose intolerance by reducing blood glucose curves in WSDF-fed mice. Evaluation of gut barrier function revealed that HD51–9 and hBD2 improve intestinal integrity by upregulating tight junction and mucin expression. Moreover, peptide treatment restored ileal host defense peptides (HDP) expression, likely by modulating the Wnt, Myd88, p38, and Jak/STAT pathways. These findings strongly suggest that α- and β-defensin treatment improve hepatic steatosis, glucose metabolism, and gut barrier function.

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Nguyen, Anh-Thu, Minho Kim, Ye-Eun Kim, Hangeun Kim, Sanghyun Lee, Yunji Lee, and Ki-Young Kim. "MSF Enhances Human Antimicrobial Peptide β-Defensin (HBD2 and HBD3) Expression and Attenuates Inflammation via the NF-κB and p38 Signaling Pathways." Molecules 28, no. 6 (March 18, 2023): 2744. http://dx.doi.org/10.3390/molecules28062744.

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Both defensin and inflammation are part of the human innate immune system that responds rapidly to pathogens. The combination of defensins with pro- or anti-inflammatory effects can be a potential research direction for the treatment of infection by pathogens. This study aimed to identify whether MSF (Miracle Synergy material made using Filipendula glaberrima), a probiotic lysate of Filipendula glaberrima extracts fermented with Lactiplantibacillus plantarum K8, activates the expression of human β-defensin (HBD2 and HBD3) to protect the host against pathogens and inhibit inflammation caused by S. aureus, in vitro with Western blot analysis, qRT-PCR and in vivo studies with a mouse model were used to evaluate the effects of MSF. The MSF treatment induced HBD2 and HBD3 expression via the p38 and NF-κB pathways. Furthermore, MSF treatment significantly reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8), also through p38 and NF-κB in S. aureus-induced inflammatory condition. MSF treatment remarkably reduced erythema in mice ears caused by the injection of S. aureus, while K8 lysate treatment did not initiate a strong recovery. Taken together, MSF induced the expression of HBD2 and HDB3 and activated anti-inflammatory activity more than the probiotic lysates of L. plantarum K8. These findings show that MSF is a potential defensin inducer and anti-inflammatory agent.

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Hamanaka, Yoichi, Masahiro Nakashima, Masahiro Ito, Akihiro Wada, Hisao Kurazono, Toshiya Hirayama, and Ichiro Sekine. "Induction of human B-defensin-2 (hBD2) in Helicobacter pylori (HP)-induced gastritis: Antibacterial effect of hBD2 against for HP." Gastroenterology 118, no. 4 (April 2000): A741. http://dx.doi.org/10.1016/s0016-5085(00)85098-2.

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Seo, Emily S., Bärbel S. Blaum, Thomas Vargues, Martin De Cecco, Jon A. Deakin, Malcolm Lyon, Perdita E. Barran, Dominic J. Campopiano, and Dušan Uhrín. "Interaction of Human β-Defensin 2 (HBD2) with Glycosaminoglycans." Biochemistry 49, no. 49 (December 14, 2010): 10486–95. http://dx.doi.org/10.1021/bi1011749.

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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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Grankovsky, V. A., E. P. Karpova, L. V. Gankovskaya, Ya S. Avalyan, E. D. Merkusheva, and E. V. Zinina. "Features of innate immunity in children with hypertrophy of the palatine tonsils." Medical Immunology (Russia) 26, no. 2 (June 7, 2023): 263–70. http://dx.doi.org/10.15789/1563-0625-foi-2650.

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Hypertrophy of pharyngeal lymphoid tissue is among the most common problems in pediatric otorhinolaryngology, in particular, hypertrophy of the palatine tonsils. This disorder is characterized by increased size of a single or both palatine tonsils combined with various clinical symptoms. The principles of treatment in children with this pathology remain debatable, since the long-term effects of bilateral tonsillotomy are still not fully understood. The aim of the study was to assess the expression levels of genes encoding the innate immunity molecules (TLR4, HBD1, HBD2, IL1β) in the mucous membranes of palatine tonsils in children with palatine tonsillitis before and after treatment.We conducted a study of 78 patients divided into three independent groups. The 1st group (comparison) included 20 somatically healthy children. The 2nd group included 28 children with grade 2 palatine tonsil hypertrophy who underwent local treatment. The 3rd group included 30 children with grade 3 hypertrophy of the palatine tonsils, who, by clinical indications, underwent bilateral tonsillotomy. Determination and evaluation of innate immunity indices was carried out both before starting the treatment, and one month later, using the real-time PCR method.In children with hypertrophy of palatine tonsils, the initial values of TLR4 gene expression and antimicrobial peptides differed from those of healthy children. A decreased expression of HBD1 and HBD2 genes, which provide immediate protection against pathogens, was revealed. The values of TLR4 gene expression differed in groups of children with varying degrees of palatine tonsillar hypertrophy. In patients with bilateral tonsillotomy, an increased expression of TLR4 gene and a decreased expression of antimicrobial peptide genes (HBD1, HBD2) were revealed, which may indicate a readiness for development of tonsillar inflammation in response to pathogens. One month after surgical treatment, the indices of innate immunity were comparable with those of healthy children thus confirming the validity of surgical treatment. In the 2nd group of patients, the TLR4 gene expression one month after conservative treatment remained reduced, the expression of β-defensin HBD1 gene increased and exceeded the indicators of the group of healthy children, the expression level of the IL-1β gene was reduced.The revealed imbalance between the TLR4, HBD1 and HBD2 expression levels confirms an important role of innate immunity mechanisms in pathogenesis of palatine tonsillitis. The assessment of innate immunity indices may be used as an additional criterion in administration of therapy for hypertrophy of palatine tonsils and evaluation of its efficiency.

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Astuti, S. D., R. Nashichah, P. Widiyanti, E. M. Setiawatie, M. S. Amir, A. Apsari, Widyastuti, et al. "Effectiveness of 650 nm red laser photobiomodulation therapy to accelerate wound healing post tooth extraction." Biomedical Photonics 13, no. 1 (May 10, 2024): 4–15. http://dx.doi.org/10.24931/2413-9432-2024-13-1-4-15.

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After tooth extraction, there can be consequences involving injury to the tissue surrounding the extracted tooth, which may lead to severe problems such as inflammation and infection. The wound healing process comprises inflammation, proliferation, and remodeling phases. Photobiomodulation is a therapy form that utilizes the interaction of a light source with tissue. This interaction can activate an increase in Adenosine Triphosphate (ATP), which subsequently triggers a chain reaction leading to the creation of new blood vessels and an increase in the number of fibroblasts. This study used a red laser light source with a power of 3.32 ± 0.01 mW, delivering a dose of 3.5 J to patients for extraction indications. The parameters observed included Interleukin 1_ (IL-1_), Prostaglandin E2 (PGE2), Human Beta defensin 2 (HBD2), and Gingival Index (GI). The results of testing saliva samples using the enzyme-linked immunosorbent test (ELISA) for the parameters IL-1_, PGE2, and HBD2 show a significant influence between the control and therapy groups. Meanwhile, GI revealed a significant influence of therapy on the wound-healing process. Using the Mann-Whitney U test, on day 1, the p-value was found to be 0.32, indicating no significant deference between the control and therapy groups. However, on the third day after the therapy was administered, the p-value was obtained as 0.01, signifying a significant deference between the control and therapy groups. On day 5, a p-value of 0.034 was obtained, signifying a significant deference between the control and therapy groups. Based on the research results, it can be observed that there is a decrease in the values of IL-1_, PGE2, HBD2, and GI. This indicates that local immune cells, including resident macrophages, are activated by pro-inflammatory mediators released in response to injury, and they play an essential role in accelerating wound healing.

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Jenke, A. C., J. Postberg, B. Mariel, K. Hensel, D. Foell, J. Däbritz, and S. Wirth. "S100A12 and hBD2 Correlate with the Composition of the Fecal Microflora in ELBW Infants and Expansion ofE. coliIs Associated with NEC." BioMed Research International 2013 (2013): 1–8. http://dx.doi.org/10.1155/2013/150372.

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Objective. To describe the development of the gut microbiota in extremely low birth weight (ELBW) infants with and without necrotizing enterocolitis (NEC) between April 2008 and December 2009, fecal microflora was prospectively analyzed in fecal samples of all ELBW infants using real-time PCR assays. In addition, fecal inflammatory were measured.Results. Fecal microflora established early in ELBW infants and microbiota composition remained stable over the first 28 days of life except for the prevalence ofC. difficilewhich decreased with decreasing antibiotic use. Infants who subsequently developed NEC had an increase of total bacterial count (9.8-fold) 24 h prior to clinical symptoms mainly due to the expansion ofE. colispecies (21.6-fold), whereas microbiota composition did not differ from healthy ELBW infants five days before onset of NEC. Importantly, S100A12 and hBD2 positively correlated with the total andE. colibacterial CFU/g feces (r20.4 and 0.64, resp.).Conclusions. In summary, we found evidence for a disturbed homeostasis between the intestinal microbiome and host immunity in ELBW infants with NEC. Moreover, S100A12 and hBD2 correlate with the fecal microbiota thus linking the intestinal innate immune response to the bacterial colonization thus possibly providing a diagnostic tool in the future.

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Arnold, M. F. F., A. F. Haag, S. Capewell, H. I. Boshoff, E. K. James, R. McDonald, I. Mair, et al. "Partial Complementation of Sinorhizobium meliloti bacA Mutant Phenotypes by the Mycobacterium tuberculosis BacA Protein." Journal of Bacteriology 195, no. 2 (November 16, 2012): 389–98. http://dx.doi.org/10.1128/jb.01445-12.

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ABSTRACTTheSinorhizobium melilotiBacA ABC transporter protein plays an important role in its nodulating symbiosis with the legume alfalfa (Medicago sativa). TheMycobacterium tuberculosisBacA homolog was found to be important for the maintenance of chronic murine infections, yet itsin vivofunction is unknown. In the legume plant as well as in the mammalian host, bacteria encounter host antimicrobial peptides (AMPs). We found that theM. tuberculosisBacA protein was able to partially complement the symbiotic defect of anS. melilotiBacA-deficient mutant on alfalfa plants and to protect this mutantin vitrofrom the antimicrobial activity of a synthetic legume peptide, NCR247, and a recombinant human β-defensin 2 (HBD2). This finding was also confirmed using anM. tuberculosisinsertion mutant. Furthermore,M. tuberculosisBacA-mediated protection of the legume symbiontS. melilotiagainst legume defensins as well as HBD2 is dependent on its attached ATPase domain. In addition, we show thatM. tuberculosisBacA mediates peptide uptake of the truncated bovine AMP, Bac71-16. This process required a functional ATPase domain. We therefore suggest thatM. tuberculosisBacA is important for the transport of peptides across the cytoplasmic membrane and is part of a complete ABC transporter. Hence, BacA-mediated protection against host AMPs might be important for the maintenance of latent infections.

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Vargues, Thomas, Gareth Morrison, Emily Seo, David Clarke, Helen Fielder, Julien Bennani, Uday Pathania, et al. "Efficient Production of Human β-Defensin 2 (HBD2) in Escherichia coli." Protein & Peptide Letters 16, no. 6 (June 1, 2009): 668–76. http://dx.doi.org/10.2174/092986609788490122.

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Deshmukh, Prashant, Shruti Mathur, Gejo Gangadharan, Gopinatha Krishnappa, Nandakumar Dalavaikodihalli Nanjaiah, and Balasundaram Padmanabhan. "Novel pyrano 1,3 oxazine based ligand inhibits the epigenetic reader hBRD2 in glioblastoma." Biochemical Journal 477, no. 12 (June 24, 2020): 2263–79. http://dx.doi.org/10.1042/bcj20200339.

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Glioblastoma (GBM) is the most common primary brain malignancy, rarely amenable to treatment with a high recurrence rate. GBM are prone to develop resistance to the current repertoire of drugs, including the first-line chemotherapeutic agents with frequent recurrence, limiting therapeutic success. Recent clinical data has evidenced the BRD2 and BRD4 of the BET family proteins as the new druggable targets against GBM. In this relevance, we have discovered a compound (pyrano 1,3 oxazine derivative; NSC 328111; NS5) as an inhibitor of hBRD2 by the rational structure-based approach. The crystal structure of the complex, refined to 1.5 Å resolution, revealed that the NS5 ligand significantly binds to the N-terminal bromodomain (BD1) of BRD2 at the acetylated (Kac) histone binding site. The quantitative binding studies, by SPR and MST assay, indicate that NS5 binds to BD1 of BRD2 with a KD value of ∼1.3 µM. The cell-based assay, in the U87MG glioma cells, confirmed that the discovered compound NS5 significantly attenuated proliferation and migration. Furthermore, evaluation at the translational level established significant inhibition of BRD2 upon treatment with NS5. Hence, we propose that the novel lead compound NS5 has an inhibitory effect on BRD2 in glioblastoma.

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Salem, Abdelhakim, Rabeia Almahmoudi, Jaana Hagström, Holger Stark, Dan Nordström, Tuula Salo, and Kari K. Eklund. "Human β-Defensin 2 Expression in Oral Epithelium: Potential Therapeutic Targets in Oral Lichen Planus." International Journal of Molecular Sciences 20, no. 7 (April 10, 2019): 1780. http://dx.doi.org/10.3390/ijms20071780.

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Human β-defensin 2 (hBD-2) is a potent antimicrobial peptide that participates in defense against invading bacteria. We recently showed that bacterial components and histamine, through histamine H4 receptor (H4R), are involved in the pathogenesis of the potentially malignant lesion, oral lichen planus (OLP). However, the underlying mechanisms remain unknown. We, therefore, investigated the role of hBD2–histamine crosstalk signaling in promoting OLP pathology. Biopsies from OLP and oral tongue squamous cell carcinoma (OTSCC) patients, and healthy controls were used. Two OTSCC cell lines and normal human oral keratinocytes (HOKs) were used. HBD-2 and other targets were mapped by immunostaining and analyzed by ImageJ2 software. The highly sensitive droplet-digital PCR technology and qRT-PCR were utilized to study the clinically derived and in vitro samples, respectively. H4R was challenged with the specific agonist HST-10 and inverse agonist ST-1007. HBD-2 was highly induced in OLP lesions. In contrast, hBD2 expression was attenuated in OTSCC tissues, while very low levels of hBD-2 messenger RNA (mRNA) were observed in OTSCC cells. Together with tumor necrosis factor-α (TNF-α), histamine upregulated hBD-2 mRNA expression in HOKs. Activation of H4R seems to modulate the expression of epithelial hBD-2. These findings suggest the involvement of hBD-2 in the pathogenesis of OLP and may, thus, be harnessed for therapeutic interventions in OLP.

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Grupp, Alexander, Martin Kimmel, Peter Fritz, Bernd Voggenreiter, Hartmut Stöltzing, Ulrich Kuhlmann, Eduard F. Stange, Thomas Mettang, Klaus Fellermann, and Dominik M. Alscher. "The Expression Patterns of Peritoneal Defensins." Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 27, no. 6 (November 2007): 654–62. http://dx.doi.org/10.1177/089686080702700611.

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Background Local defense mechanisms are important for the integrity of the peritoneum, but few details are known about the expression patterns of antimicrobial proteins such as human defensin in normal and damaged peritoneum. Methods Part A: The expression of different defensins in normal ( n = 12), inflamed ( n = 5), and metastatic peritoneum ( n = 4) and in cultured human peritoneal mesothelial cells was analyzed using mRNA and immunohistochemistry. Part B: Using immunohistochemistry the expression of different defensins was analyzed in different subgroups: healthy controls ( n = 25), patients with chronic appendicitis ( n = 25) or acute appendicitis ( n = 10), and end-stage renal disease patients ( n = 25, with 15 on peritoneal dialysis). Results Part A: Human neutrophil peptides (HNP) 1 and 3 and human β-defensins (HBD) 1 to 3 mRNA were detected in peritoneal specimens. In addition, HNP1,3, HBD1, HBD2, and HBD3 proteins were detected using immunohistochemistry. Part B: HBD1 showed a constitutive expression in mesothelium, while HBD2 and HNP1,3 were associated with inflammation. Decreased expressions of HNP1,3 were observed in end-stage renal disease patients and in patients on peritoneal dialysis. Conclusions For the first time, the expression patterns of defensins in normal and damaged peritoneum have been described. The reduced expression of some defensins in end-stage renal disease is of potential clinical interest against the background of the frequent infective complications seen in peritoneal dialysis.

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Kim, MinJeong, Kui Young Park, Mi-Kyung Lee, Taewon Jin, and Seong Jun Seo. "Adiponectin Suppresses UVB-Induced Premature Senescence and hBD2 Overexpression in Human Keratinocytes." PLOS ONE 11, no. 8 (August 15, 2016): e0161247. http://dx.doi.org/10.1371/journal.pone.0161247.

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Kim, MinJeong, Kui Young Park, Mi-Kyung Lee, Taewon Jin, and Seong Jun Seo. "Correction: Adiponectin Suppresses UVB-Induced Premature Senescence and hBD2 Overexpression in Human Keratinocytes." PLOS ONE 11, no. 9 (September 6, 2016): e0162738. http://dx.doi.org/10.1371/journal.pone.0162738.

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Li, Jing, Michael Raghunath, Donald Tan, Ricky R. Lareu, ZhenCheng Chen, and Roger W. Beuerman. "Defensins HNP1 and HBD2 Stimulation of Wound-Associated Responses in Human Conjunctival Fibroblasts." Investigative Opthalmology & Visual Science 47, no. 9 (September 1, 2006): 3811. http://dx.doi.org/10.1167/iovs.05-1360.

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Yamamoto, Eiji, Tomonori Takashi, Yoichi Morinaka, Shaoyang Lin, Hidemi Kitano, Makoto Matsuoka, and Motoyuki Ashikari. "Interaction of two recessive genes, hbd2 and hbd3, induces hybrid breakdown in rice." Theoretical and Applied Genetics 115, no. 2 (May 9, 2007): 187–94. http://dx.doi.org/10.1007/s00122-007-0554-9.

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White, John H. "Emerging Roles of Vitamin D-Induced Antimicrobial Peptides in Antiviral Innate Immunity." Nutrients 14, no. 2 (January 11, 2022): 284. http://dx.doi.org/10.3390/nu14020284.

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Vitamin D deficiency, characterized by low circulating levels of calcifediol (25-hydroxyvitamin D, 25D) has been linked to increased risk of infections of bacterial and viral origin. Innate immune cells produce hormonal calcitriol (1,25-dihydroxyvitamin D, 1,25D) locally from circulating calcifediol in response to pathogen threat and an immune-specific cytokine network. Calcitriol regulates gene expression through its binding to the vitamin D receptor (VDR), a ligand-regulated transcription factor. The hormone-bound VDR induces the transcription of genes integral to innate immunity including pattern recognition receptors, cytokines, and most importantly antimicrobial peptides (AMPs). Transcription of the human AMP genes β-defensin 2/defensin-β4 (HBD2/DEFB4) and cathelicidin antimicrobial peptide (CAMP) is stimulated by the VDR bound to promoter-proximal vitamin D response elements. HDB2/DEFB4 and the active form of CAMP, the peptide LL-37, which form amphipathic secondary structures, were initially characterized for their antibacterial actively. Notably, calcitriol signaling induces secretion of antibacterial activity in vitro and in vivo, and low circulating levels of calcifediol are associated with diverse indications characterized by impaired antibacterial immunity such as dental caries and urinary tract infections. However, recent work has also provided evidence that the same AMPs are components of 1,25D-induced antiviral responses, including those against the etiological agent of the COVID-19 pandemic, the SARS-CoV2 coronavirus. This review surveys the evidence for 1,25D-induced antimicrobial activity in vitro and in vivo in humans and presents our current understanding of the potential mechanisms by which CAMP and HBD2/DEFB4 contribute to antiviral immunity.

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Porter, Edith, Huixia Yang, Sujata Yavagal, Gloria C. Preza, Omar Murillo, Heriberto Lima, Sheila Greene, et al. "Distinct Defensin Profiles in Neisseria gonorrhoeae and Chlamydia trachomatis Urethritis Reveal Novel Epithelial Cell-Neutrophil Interactions." Infection and Immunity 73, no. 8 (August 2005): 4823–33. http://dx.doi.org/10.1128/iai.73.8.4823-4833.2005.

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ABSTRACT Defensins are key participants in mucosal innate defense. The varied antimicrobial activity and differential distribution of defensins at mucosal sites indicate that peptide repertoires are tailored to site-specific innate defense requirements. Nonetheless, few studies have investigated changes in peptide profiles and function after in vivo pathogen challenge. Here, we determined defensin profiles in urethral secretions of healthy men and men with Chlamydia trachomatis- and Neisseria gonorrhoeae-mediated urethritis by immunoblotting for the epithelial defensins HBD1, HBD2, and HD5 and the neutrophil defensins HNP1 to -3 (HNP1-3). HBD1 was not detectable in secretions, and HBD2 was only induced in a small proportion of the urethritis patients; however, HD5 and HNP1-3 were increased in C. trachomatis infection and significantly elevated in N. gonorrhoeae infection. When HNP1-3 levels were low, HD5 appeared mostly as the propeptide; however, when HNP1-3 levels were >10 μg/ml, HD5 was proteolytically processed, suggesting neutrophil proteases might contribute to HD5 processing. HD5 and HNP1-3 were bactericidal against C. trachomatis and N. gonorrhoeae, but HD5 activity was dependent upon N-terminal processing of the peptide. In vitro proteolysis of proHD5 by neutrophil proteases and analysis of urethral secretions by surface-enhanced laser desorption ionization substantiated that neutrophils contribute the key convertases for proHD5 in the urethra during these infections. This contrasts with the small intestine, where Paneth cells secrete both proHD5 and its processing enzyme, trypsin. In conclusion, we describe a unique defensin expression repertoire in response to inflammatory sexually transmitted infections and a novel host defense mechanism wherein epithelial cells collaborate with neutrophils to establish an antimicrobial barrier during infection.

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Corrales-García, Ligia Luz, Leobardo Serrano-Carreón, and Gerardo Corzo. "Improving the heterologous expression of human β-defensin 2 (HBD2) using an experimental design." Protein Expression and Purification 167 (March 2020): 105539. http://dx.doi.org/10.1016/j.pep.2019.105539.

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Stanton, A., A. S. M. Ali, R. S. Pickard, and J. Hall. "140 Estrogen and hBD2 in the innate defence of the female uro-genital tract." European Urology Supplements 14, no. 2 (April 2015): e140. http://dx.doi.org/10.1016/s1569-9056(15)60142-7.

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Zhong, Zhixia, Zhinan Xu, Li Peng, Lei Huang, Xiangming Fang, and Peilin Cen. "Tandem repeat mhBD2 gene enhance the soluble fusion expression of hBD2 in Escherichia coli." Applied Microbiology and Biotechnology 71, no. 5 (December 2, 2005): 661–67. http://dx.doi.org/10.1007/s00253-005-0212-6.

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ZONG, Zhao-Wen, Nan LI, Tao-Yuan XIAO, Yong-Ping SU, Shi-Wu DONG, Jun-Ping WANG, Lian-Yang ZHANG, Yue SHEN, Chun-Meng SHI, and Tian-Min CHENG. "Effect of hBD2 Genetically Modified Dermal Multipotent Stem Cells on Repair of Infected Irradiated Wounds." Journal of Radiation Research 51, no. 5 (2010): 573–80. http://dx.doi.org/10.1269/jrr.10047.

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Li, Jing, Hong Yuan Zhu, and Roger W. Beuerman. "Stimulation of Specific Cytokines in Human Conjunctival Epithelial Cells by Defensins HNP1, HBD2, and HBD3." Investigative Opthalmology & Visual Science 50, no. 2 (February 1, 2009): 644. http://dx.doi.org/10.1167/iovs.08-1838.

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Lafferty, Mark K., Lingling Sun, Wuyuan Lu, and Alfredo Garzino-Demo. "112 hBD2 inhibits HIV via CCR6, a receptor expressed on memory, Dendritic and Th17 cells." JAIDS Journal of Acquired Immune Deficiency Syndromes 51 (June 2009): 1. http://dx.doi.org/10.1097/01.qai.0000351069.36343.fa.

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Ostaff, Maureen J., Sabrina R. Stebe-Frick, Eduard F. Stange, Nisar P. Malek, and Jan Wehkamp. "HDAC Mediated Regulation of the Antimicrobial HBD2 Differs between Intestinal Cell Lines and Cultured Tissue." Gastroenterology 152, no. 5 (April 2017): S999. http://dx.doi.org/10.1016/s0016-5085(17)33388-7.

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Witthoeft, T. "Dexamethasone induced upregulation of human beta-defensin-2 (HBD2) mRNA expression in human colonic epithelial cells." Inflammatory Bowel Diseases 14 (January 2008): S38. http://dx.doi.org/10.1097/00054725-200801001-00135.

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Witthoeft, T. "Dexamethasone induced upregulation of human beta-defensin-2 (HBD2) mRNA expression in human colonic epithelial cells." Inflammatory Bowel Diseases 14 (February 2008): S37. http://dx.doi.org/10.1097/00054725-200802001-00135.

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Journal articles on the topic 'HBND2'

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