Dissertations / Theses on the topic 'Chemokine biology'
To see the other types of publications on this topic, follow the link: Chemokine biology.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Chemokine biology.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Maru, Seema V. "The role of chemokines and chemokine receptors in astrocytes and astrocytoma biology." Thesis, Open University, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427496.
Full text
2
Millette, Roxanne. "The effect of chemokine CCL19 on B lymphocytes /." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=79051.
Full textAbstract:
B-T lymphocyte interaction within lymphoid tissues following antigen exposure is a crucial step in the generation of high affinity antibody. Due to its expression pattern and specificity for B lymphocytes, CC Chemokine Ligand 19 (CCL19) may help initiate the adaptive humoral immune response following antigen exposure. Here we show CCL 19 induced [Ca2+]i mobilization, chemotaxis and rescue from apoptosis in B lymphocytes. Because CCL19 is constitutively expressed, we studied the expression and signalling properties of its corresponding chemokine receptor, CC chemokine receptor 7 (CCR7) in various B cell populations. We found that CCL19 responsive CCR7 + cells belonged to distinct B lymphocyte populations at particular stages of maturation and that BCR crosslinking alone was insufficient to modulate CCR7 expression and CCL19 responsiveness. CCL19 induced signal transduction events were Galphai dependent. We found that CCL19 stimulation could desensitize the CCR7 receptor to further CCL19 stimulation, but did not interfere with other key B cell activation signals such as BCR and PAF. Our results implicate CCL19 in B lymphocyte activation, migration, and survival.
3
Finley, Matthew James. "Molecular Basis for Kappa-Opioid Regulation of Chemokine Receptor Function." Diss., Temple University Libraries, 2009. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/62878.
Full textAbstract:
Molecular Biology and GeneticsPh.D.
Opioid receptor-mediated regulation of chemokine receptors is vital for the host immune response, development, and neurological function. Previous studies have demonstrated that the kappa opioid receptor (KOR) activation results in decreased infectivity of human immunodeficiency virus 1 (HIV-1) in human peripheral blood mononuclear cells (PBMCs). We have found this effect is due to down-regulation of the major HIV-1 co-receptors, CCR5 and CXCR4. Using molecular techniques, CCR5 and CXCR4 mRNA levels drop dramatically following KOR activation. To dissect the mechanism involved, we used transcription factor binding arrays and compared control cell extracts to KOR activated cell extracts. We determined that the interferon regulatory factors (IRFs) and signal transducers and activators of transcription (STATs) could be involved in the KOR-mediated repression of CCR5 and CXCR4 transcription and protein expression. Using chemical inhibitors and small interfering RNA (siRNA) molecules, we determined that JAK2, STAT3, and IRF2 are critical members of this signal transduction pathway. The understanding of these particular mechanisms should prove to be beneficial for the development of potential pharmacological agents targeted at HIV-1 binding and infection since virus infection requires expression of the co-receptors CXCR4 and CCR5. Understanding the molecular basis for KOR-induced inhibition of co-receptor expression may provide a basis for the development of KOR agonist-based therapeutics to treat individuals infected with HIV.
Temple University--Theses
4
Zhu, John Z. "Sulfotyrosines impart ligand specificity in a chemokine receptor model system." [Bloomington, Ind.] : Indiana University, 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3380144.
Full textAbstract:
Thesis (Ph.D.)--Indiana University, Dept. of Biochemistry, 2009.Title from PDF t.p. (viewed on Jul 20, 2010). Source: Dissertation Abstracts International, Volume: 70-12, Section: B, page: 7377. Advisers: Martin J. Stone; Carl E. Bauer.
5
Tiplady, Eleanor Margaret. "Expression and modulation of atypical chemokine receptors on epithelial cells." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/30618/.
Full textAbstract:
The immune system relies on the correct spatial and temporal positioning of cells in order to function; cells need to be able to move throughout the circulatory system to survey for pathogens, to migrate from their resident sites in tissues when they sense infection or injury to alert other cells, or to migrate to the site of damage or infection to help mobilise a response. These functions often involve chemokines, small cytokines that signal through chemokine receptors, which are G-protein coupled receptors expressed on the cell membrane. Different chemokines are regulated differentially and can be associated with certain tissues or developmental processes, meaning the suite of receptors expressed by each cell type determines which tissues it is capable of entering, and the precise location it takes up once inside the tissue. Atypical chemokine receptors are a class of chemokine receptors that do not initiate the downstream signalling pathways typical of a G-protein coupled receptor, as they do not recruit intracellular G-proteins, and generally don't induce cell migration. Instead, these receptors are thought to function mainly as chemokine scavenging receptors, internalising and destroying their ligands before rapidly recycling to the cell surface. In this way, the levels of chemokines in the body are prevented from becoming oversaturated thus dampening the ability of cells to respond to signals. ACKR3 and ACKR4 are two atypical chemokine receptors that are expressed on endothelial cells and keratinocytes in the skin. Here, I have studied their expression on cultured human lymphatic endothelial cells and keratinocytes, and modulation in response to immune stimuli on these cells using a combination of qPCR and immunofluorescent staining. These strategies revealed that ACKR3 and ACKR4 are expressed on cultured LECs and keratinocytes and may be differentially regulated by both cell types in response to inflammatory stimuli including bacterial (LPS) and viral (Unmethylated CpG DNA) signatures. Although chemokine scavenging activity could not be detected on these cells, these findings suggested a role for ACKRs 3 and 4 in the inflammatory response. Further experiments in vivo explored the expression and modulation of ACKR3/CXCR4 and ACKR4 on epithelial cells including lymphatic endothelial cells, keratinocytes and vascular endothelial cells in the spleen. Flow cytometry was used to examine tissues both at rest and after inflammation (Aldara-mediated psoriasis model, or TPA-mediated contact hypersensitivity model) and investigate the regulation of ACKR3/CXCR4 or ACKR4 in response to these stimuli. Key findings included the strong overlap and differential regulation of ACKR3 and CXCR4 in response to TPA in the infundibulum subset of keratinocytes. Additionally, lymph nodes of Ackr4-/- mice were significantly enlarged after repeated treatments with Aldara. This appeared to be due to CCL19 dysregulation, but adoptive transfer suggested that there was no defect in leukocyte homing in these mice. This suggested an as yet undetermined response to enhanced CCL19 bioavailability that did not prevent the correct migration of leukocytes to secondary lymphoid organs. Overall, these experiments suggested that ACKR3 and ACKR4 are modulated in response to several inflammatory stimuli both in vivo and in vitro, and that the modulation of homeostatic chemokines can play a role in the response to inflammatory events. This was particularly important in the context of skin inflammation, where inflammatory chemokines, CXCR4 and ACKR2 have all been implicated in severity and duration of inflammatory events, but few studies have yet described the potential contributions of ACKR3 or ACKR4.
6
Randolph-Habecker, Julie. "The expression and function of the human cytomegalovirus encoded beta-chemokine receptor homolog, US28 /." The Ohio State University, 1998. http://rave.ohiolink.edu/etdc/view?acc_num=osu148795159550182.
Full text
7
Cook, Sarah Louise. "The role of CC-chemokine receptor-like 2 in the B cell response." Thesis, University of Birmingham, 2015. http://etheses.bham.ac.uk//id/eprint/5645/.
Full textAbstract:
CCRL2 is a member of the atypical chemattractant family. It has been proposed to bind the chemokines CCL19 and CCL5, as well as the adipokine chemerin. Unlike typical chemokine receptors, atypical chemoattractant receptors do not undergo conventional G protein signalling upon binding, but instead degrade, transcytose or present their ligands on the cell surface. This study aims to characterise the role of CCRL2 in B cells upon their activation and differentiation into either extrafollicular plasmablasts or germinal centre B cells. CCRL2 mRNA is upregulated upon plasmablast differentiation. Upon immunisation with NP-Ficoll, CCRL2 deficient mice produce more NP-specific antibody and larger numbers of NP-specific plasmablasts. Further assessment show this phenotype is due to B cell intrinsic effects. CCRL2 deficient plasmablasts tend to proliferate more and undergo less apoptosis than CCRL2 expressing plasmablasts. The role of CCRL2 in the germinal centre was also assessed. Germinal centres formed normally, including polarisation into light and dark zones in CCRL2 deficient mice. However, FDCs within the germinal centre appeared to extend further into the follicular mantle in CCRL2 deficient mice. This may be the cause of an increased proportion of germinal centres over the whole spleen in CCRL2 deficient mice. These differences did not result in significant changes in affinity maturation. Together, this shows a novel role for CCRL2 in the regulation of the extrafollicular plasmablast response to NP-Ficoll. However, minor differences in CCRL2 deficient germinal centres do not affect high affinity plasma cell output, suggesting a minimal role of CCRL2 in GC function.
8
Mukhi, Sumedha. "Effects of Chronic Morphine Administration on Cytokine & Chemokine Protein and Gene Expression." Master's thesis, Temple University Libraries, 2012. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/214787.
Full textAbstract:
Molecular Biology and GeneticsM.S.
Chemokine and chemokine receptors play a major role in HIV-1 infectivity, and their expression can be modulated by opioid drugs of abuse, further implicating a role for these drugs in altering HIV-1 susceptibility. Several of the opioid agonists including morphine and heroin impair resistance to a variety of infectious agents including HIV-1 by modulating both innate and acquired immune responses. The aim of my thesis is to understand whether chronic morphine administration alters the expression of pro-inflammatory cytokines and chemokines. Since there are limited reports in the literature describing the effects of chronic opioid administration on immune competence, a macaque model was devised to analyze the immune system following chronic morphine administration. My results show that animals receiving morphine exhibit enhanced proinflammatory CXCL8 protein expression in response to stimulation with various Toll Receptor (TLR) ligands. This result was observed in responses to either the combination of LPS and IFNγ, or with the TLR ligand peptidoglycan. These results suggest that chronic morphine administration increases immune system responsiveness. We extended these studies on opioid-induced signaling and gene expression in human subjects and observed that opioid treatment induces the expression of CXCL10, TLR4, and the aryl hydrocarbon receptor (AHR) in leukocytes early in response to treatment. In sum, I have shown that opioid agonists modulate important immune-response genes, and these genes are important for the generation of antimicrobial immunity.
Temple University--Theses
9
Jung, Jaeho. "Cytokine and chemokine gene expression during influenza virus infection, and the effects of restraint stress /." The Ohio State University, 1996. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487942182322557.
Full text
10
Qu, Yiding. "Role of non-signaling (decoy) chemokine receptors in regulating cell migration: the mathematical model." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114337.
Full textAbstract:
Chemokines belong to a family of important chemoattractants that guide the directional migration of the cell. The cognate chemokine receptor on the cell senses the chemokine gradient and the cell moves towards the signal of increasing chemokine concentration. However, several chemokine receptors were recently identified as non-signaling (decoy), based on their ability to bind the chemokine but produce no measurable signal for the cell. The function of these decoy receptors is yet unknown. We hypothesized that the ligand binding by the decoy receptor may help maintaining a sharper chemokine gradient and thus stimulate the cell migration. We first assessed if the expression of decoy and corresponding signaling receptors changes when cancer cells acquire migratory phenotype – become metastatic. Using publically available database of gene expression in normal prostate, carcinoma and metastatic prostate cancer samples, we have found that the expression of decoy receptors CCX-CKR and OPG increased in metastatic cancer cells compared to normal prostate and positively correlated with the expression of signaling receptors CCR7 and RANK respectively. We next developed mathematical model that described the dynamics of chemokine ligand, normal receptor and decoy receptor as well as subsequent cell movement. Using this model we first assessed how the cells expressing signaling receptors only migrate towards the source of ligand given at different concentrations. At low levels of ligand, cell migration increased with the increase in ligand concentration. However, at higher concentrations, when the ligand levels exceeded the signaling receptor capacity, further increase in ligand resulted in the decrease the distance of cell migration. Importantly, at high levels of ligand the presence of the decoy receptor improved the speed and distance of cell migration. This study suggests the novel function for the non-signaling chemokine receptors in maintaining the chemokine gradient and positively regulating directional cell migration.Les chimiokines appartiennent à une importante famille de ligands chimiotactiques qui guident la direction migratoire des cellules. Sur une cellule-cible, des récepteurs spécifiques à une chimiokine donnée répondent à un gradient du ligand, provoquant la migration cellulaire vers le signal avec une concentration croissante. Cependant, quelques récepteurs pouvant liés des chimiokines ont récemment été identifiés comme muets (leurre) parce que la liaison du ligand ne stimule pas de signalisation mesurable dans la cellule. La fonction de ces récepteurs-leurres n'est pas connue actuellement.Nous avons émis l'hypothèse que l'interaction des chimiokines à ces récepteurs-leurres contribue à maintenir un gradient de ligand plus prononcé et donc stimule les cellules à migrer. Afin de tester cette hypothèse, nous avons en premier comparé l'expression de récepteurs signalant et de récepteurs-leurres pour un même ligand, quand des cellules deviennent métastatiques. En utilisant des bases de données publiques sur l'expression des gènes dans des échantillons de prostate normale, de carcinomes prostatiques, et de métastases prostatiques, nous avons remarqué que l'expression des récepteurs-leurres CCX-CKR et OPG est augmentée dans les cellules métastatiques lorsque comparée avec les cellules de prostate normales. Nous avons aussi trouvé une corrélation positive avec les niveaux d'expression des récepteurs signalants CCR7 et RANK. Par la suite, nous avons développé un modèle mathématique qui prédit la dynamique des concentrations de chimiokines, l'expression des récepteurs signalants, des récepteurs-leurres, et des mouvements de la cellule résultants. Nous avons tout d'abord utilisé ce modèle afin de prédire comment des cellules exprimant seulement des récepteurs signalant migrent vers la source du ligand selon sa concentration. En présence de faibles concentrations de ligand, la migration cellulaire augmente proportionnellement à l'augmentation de la concentration du ligand. Cependant, à des concentrations plus élevées dépassant la capacité de liaison du récepteur signalant, une augmentation subséquente diminue la distance migrée par la cellule. L'expression concomittante de récepteurs-leurres améliore la vitesse et la distance de la migration cellulaire lorsque la concentration du ligand est élevée. Cette étude suggère donc que les récepteurs-leurres des chimiokines contribuent au gradient chimiotactique et augmentent la migration des cellules.
11
Godbout, Marianne. "Role of toll-like receptor 4 in Leishmania-induced chemokine gene expression and inflammatory response." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82242.
Full textAbstract:
Modulation of the innate immune response by Leishmania has been extensively studied; however, some questions still need to be answered. In the present study, we demonstrated, in vitro and in vivo, that Leishmania interacts with TLR4 in order to induce chemokine mRNA expression. That TLR4-dependent macrophage (M&phis;) activation was shown to be MyD88-independent in vitro, and results in the activation of the transcription factors NF-kappaB and CREB. Their role in chemokine mRNA expression was further demonstrated using specific inhibitors toward these transcription factors. Moreover, using TLR4-deficient mice we confirmed the role of TLR4 in Leishmania-induced chemokine gene expression and in the subsequent recruitment of inflammatory cells. Collectively, our results bring new insights for understanding the interaction of Leishmania with its host cell, the M&phis;.
12
Happel, Christine. "Molecular Basis for Mu-Opioid Regulation of Chemokine Gene Expression." Diss., Temple University Libraries, 2009. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/28438.
Full textAbstract:
Molecular Biology and GeneticsPh.D.
Opioid receptor modulation of pro-inflammatory cytokine production is vital for host defense and the inflammatory response. Previous results have shown the mu-opioid receptor (MOR) selective agonist, DAMGO, has the capacity to increase the expression of the pro-inflammatory chemokines, CCL2/MCP-1, CCL5/RANTES and CXCL10/IP-10 in peripheral blood mononuclear cells (PBMCs). We have shown that MOR activation is able to induce the expression of TGF-β, and TGF-β appears to be required for induction of CCL5 following MOR activation. This work suggests a novel role for TGF-β in the inflammatory response. NF-κB is a transcription factor that plays a pivotal role in inflammation and the immune response. We have found that NF-kB inhibitors can prevent the MOR-induced activation of CCL2 and CCL5, and that the NF-kB subunit, p65, is phosphorylated at serine residues 311 and 536 in response to μ-opioid receptor activation. In vivo, DAMGO administration can induce binding of p. 65 to the enhancer region of the CCL2 promoter. Furthermore, we demonstrate that PKCζ is phosphorylated following DAMGO-induced MOR activation and, is essential for NF-kB activity as well as CCL2 expression and transcriptional activity. In conclusion, these data suggest a pro-inflammatory role for MOR which involves NF-κB activation and PKCζ as well as a novel role for TGF-β as a regulator of pro-inflammatory chemokines.
Temple University--Theses
13
Eshaque, Shathi. "Functional Characterization of Rainbow Trout (Oncorhynchus mykiss) Chemokine 2 (CK-2)." Thesis, University of Waterloo, 2006. http://hdl.handle.net/10012/1271.
Full textAbstract:
Chemokines are cytokines with chemoattractant ability, and comprise one of the major groups of molecules in immune system. These are small, secreted proteins cause the migration of leukocytes to the sites of injury. Over 40 mammalian chemokines have been identified to date, and they have been implicated in a number of immune mediated processes, including regulation of inflammation, antigen presentation, blood cell development, metastasis, viral infection and wound healing. In rainbow trout, there have been fewer chemokines reported and only one functional study has been published. Rainbow trout chemokine 2 (CK-2) is the only known CC chemokine with a mucin stalk, which has the potential for extensive O-glycosylation. However, no functional characterization has been performed on this molecule yet. CK-2 shares the presence of a mucin stalk with the mammalian chemokines, fractalkine (CX3CL1), lymphotactin (XCL1), and CXCL16. Another related trout CC chemokine sequence, CK-2. 1, has been discovered recently, which has 98% nucleotide sequence identity with CK-2. CK-2. 1 was believed to be a separate gene due to its apparent differential regulation in challenged rainbow trout. The question remained, however, whether or not CK-2. 1 was a separate gene or an allele of CK-2. The goal of this project was to further characterize both CK-2 and CK-2. 1. Through genomic PCR on several outbred individuals it was shown that CK-2. 1 is an allele of CK-2 but not a separate gene. Reverse transcriptase (RT) PCR analysis revealed an increased level of transcript both CK-2 and CK-2. 1 in response to phytohaemagglutinin (PHA) stimulation of head kidney leukocytes (HKL) and peripheral blood leukocytes (PBL) collected from fish with different allelic distributions. Similar results were also observed in the rainbow trout macrophage/monocyte cell line, RTS11. Moreover, an anti-CK-2 antiserum was developed in rabbits, which cross-reacted with CK-2. 1. This newly produced antibody was used to determine the protein expression levels in PHA stimulated rainbow trout tissues. RT-PCR was also performed on the same tissues in order to examine the transcript expression. Rainbow trout with both CK-2 and CK-2. 1 were used for this experiment. An overall decreasing pattern of transcript (both CK-2 and CK-2. 1) was observed in brain and HK over 24 hours, while protein was still detected at 24 hours post stimulation. However, in spleen the CK-2 transcript showed a slight upregulation at 4 hours post stimulation along with a very little or no CK-2. 1 expression, although no protein was detected in spleen. Liver showed a very low level of CK-2 and CK-2. 1 transcript at 8 hours post stimulation; while protein was again detected at 24 hours post stimulation. In addition, the sizes of the proteins found in different tissues were larger than expected (≤30 kDa for CK-2 or ≤35 for CK-2. 1), perhaps due to the presence of extensive O-glycosylation at the mucin stalk of the protein.
A chemotaxis assay was carried out, which is the definitive assay for chemokine activity. This assay showed migration of peripheral blood leukocytes across a membrane with 5µm pores toward CK-2 at an optimal concentration of 500ng/ml (17nm). Moreover, by pre-treating the recombinant chemokine with the polyclonal antisera, it was shown that the chemokine was actually causing the chemotactic activity. Pre-treatment of the cells with pertussis toxin, an inhibitor of G-protein signalling inhibited the migration of PBLs, established the fact that CK-2 caused chemotaxis by binding to a 7 transmembrane, G-coupled receptor just like all other known chemokines. Interestingly, CK-2 was also shown to attract RTS-11 cells.
Overall, the above findings indicate that CK-2 is functionally a chemokine with two very different alleles in rainbow trout. It is probably heavily O-glycosylated and different tissues express different sizes of the protein. This is only the second functional study of a fish chemokine.
14
Heinisch, Silke. "Chemokine interactions with the serotonin and opioid systems: anatomical and electrophysiological studies in the rat brain." Diss., Temple University Libraries, 2008. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/9181.
Full textAbstract:
AnatomyPh.D.
Chemokines, immune proteins that induce chemotaxis and adhesion, and their G-protein coupled receptors distribute throughout the central nervous system (CNS), regulate neuronal patterning, and mediate neuropathology. These chemo-attractant molecules may provide a neuro-immune "link" by regulating CNS systems. The purpose of this study was to investigate the interactions of specific chemokines, stromal cell-derived factor (SDF)-1a/CXCL12, and fractalkine/CX3CL1, and their receptors, CXCR4 and CX3CR1, with the serotonin (5-hydroxytryptamine; 5-HT) and opioid systems using anatomical and electrophysiological techniques in the rat brain. In the serotonin dense midbrain raphe nuclei (RN), SDF-1a, CXCR4, fractalkine and CX3CR1 co-localize over 70% with 5-HT neurons. CX3CR1 also localizes to microglia in the RN and hippocampus. Functionally, SDF-1a (10 nM) increases spontaneous inhibitory postsynaptic current (sIPSC) frequency and evoked IPSC (eIPSC) amplitude, while decreasing paired-pulse ratio (PPR) selectively in 5-HT neurons, thus stimulating presynaptic GABA release at these neurons. Alternatively, fractalkine (10 nM) increases sIPSC and eIPSC amplitude without changing PPR selectively in 5-HT neurons, thereby elevating the postsynaptic GABA receptor number or sensitivity. These results are dose-dependent and receptor-mediated. Chemokine interactions with serotonin, a neurotransmitter regulating mood, may lead to therapies for depression comorbid with immune diseases. Additional immunohistochemical analysis in the brain shows CXCR4 and CX3CR1 neuronal co-localization with the mu-opioid receptor (MOR) in the hippocampus, cingulate cortex, periaqueductal grey (PAG), nucleus accumbens, ventral tegmental area, globus pallidus, but not in the striatum or habenular nuclei, suggesting region specific receptor interactions. Electrophysiological recordings following morphine, SDF-1?? or fractalkine in vitro treatment reveal morphine (10 ?M)-mediated hyperpolarization of the membrane potential and reduction of the input resistance of PAG neurons, however, SDF-1??and fractalkine at 10 nM do not impact either parameter. In combination, SDF-1? inhibits morphine's actions in all PAG neurons tested, and fractalkine blocks morphine-mediated changes in 60% of PAG neurons examined. Thus, CXCR4 as well as CX3CR1, although less consistently, both appear to desensitize MOR at the neuronal level. Chemokine-opioid receptor interactions may mediate novel mechanisms to treat neuro-inflammatory pain and opiate abuse. The combined anatomical and electrophysiological results support chemokines as neuromodulatory proteins that may provide communication between the nervous and immune systems.
Temple University--Theses
15
Rojas-Rudolph, Isolde Gina. "Stress modulation of susceptibility to wound infection : effects on Leukocyte Trafficking and Chemokine Gene Expression during Cutaneous Wound Healing /." The Ohio State University, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=osu1486474078047403.
Full text
16
Kontolemos, Mario. "Chemokine receptors on airway epithelial cells and their potential role in regulating mucin production." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=78396.
Full textAbstract:
Chemokines, small molecular weight chemotactic cytokines, are produced mostly by airway epithelial cells and are known to play an instrumental role in the recruitment of inflammatory cells. Studies have documented a dramatic increase in the chemokine levels in the airways of asthmatics and many other studies have shown the induction of these chemokines by cytokines and growth factors in airway epithelial cells in vitro. Thus, given the high levels of chemokines in asthmatic airways and abundant evidence supporting strong interactions between cytokines and epithelial cells, we hypothesized that chemokine receptors are present on airway epithelium, and that chemokines may act through these receptors to increase mucin production. Here we demonstrate constitutive expression of chemokine receptors CCR3, CCR5 and CXCR4 in the A549 cell line by Western blot and RT-PCR.The results of this study show that chemokine receptors are present on airway epithelial cells and that chemokines may act as a stimulus for epithelial cell mucin gene expression. Our novel finding that several CC chemokines upregulate the expression of MUC5AC mRNA might be an important mechanism regulating airway epithelial cell phenotype and function under conditions of inflammation in asthma.
17
Crisman, Jacqueline M. "Identification of amino acids that are responsible for the binding of macrophage inflammatory protein-1 [alpha] to the ckr1 chemokine receptor /." The Ohio State University, 1997. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487948158625889.
Full text
18
Guan, Ping. "Identification, genomic structure, and functional studies of the human novel CC chemokine MIP-4, and the cloning of the murine homologue /." The Ohio State University, 1998. http://rave.ohiolink.edu/etdc/view?acc_num=osu148795320428111.
Full text
19
Coke, Christopher James. "Cannabinoid Receptor 2 and C-X-C Chemokine Receptor 4 Interact to Abrogate CXCL12-Mediated Cellular Response." DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2017. http://digitalcommons.auctr.edu/cauetds/76.
Full textAbstract:
The expression of C-X-C Chemokine Receptor 4 (CXCR4) has been correlated with increased metastatic potential of cancer cells. CXCR4 increases tumor malignancy by encouraging tumors cells to migrate to distal organs expressing its cognate ligand, CXCL12, facilitating metastasis. Thus, targeting the CXCR4/CXCL12 signaling axis provides a good strategy to inhibit the metastatic spread of tumor cells and slow cancer progression. Various studies suggest that cannabis may have anti-proliferative as well as anti-metastatic properties, though a biochemical mechanism describing how this occurs has yet to be discovered. Our lab has confirmed that agonist-bound CXCR4 and agonist-bound Cannabinoid Receptor 2 (CB2) can form heterodimers that play a role in decreasing cancer cell migration. Simultaneous treatment of the breast cancer cell line, MDA-MB-231 and the prostate cancer cell line PC-3, with CXCL12 and AM1241, a synthetic ligand for CB2, desensitizes the intrinsic cellular response to migrate toward areas of high CXCL12 concentration. Furthermore, through co-immunoprecipitation and
proximity ligation assays (PLA), we have determined that there is increased interaction between the two receptors with co-stimulation of respective agonists, providing evidence for the therapeutic notion that treating tumors that endogenously secrete CXCL12 with exogenous ligands for the cannabinoid can induce dimerization. Moreover, when CXCR4 and CB2 were activated simultaneously with various agonists, decreases in migration were observed, confirming that the regulatory activity was receptor-based, not agonist-based. Finally, to determine whether simultaneously–treated, dimerized receptors inhibited activity of respective receptors, calcium mobilization assays to determine G-protein coupled receptor activation were employed. Results showed that transiently activated calcium levels were significantly lower in response to simultaneous treated cells when compared to cells treated with their individual ligands. Phosphorylation of ERK and AKT were abrogated in response to simultaneous stimulation indicating loss in downstream signaling. Therefore, we believe that the interaction of CB2 with CXCR4 may play a role in inhibiting the cells response to CXCL12, leading to a loss in metastatic potential of cells expressing these receptors.
20
Padovani-Claudio, Dolly Ann. "FUNCTIONAL ANALYSES OF THE CHEMOKINE RECEPTOR CXCR2 IN THE NORMAL AND DEMYELINATED ADULT CENTRAL NERVOUS SYSTEM." Case Western Reserve University School of Graduate Studies / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=case1152193193.
Full text
21
Paccione, Kristin E. "Cytokine and Chemokine Profiles in a Rat Model of Hemorrhagic Shock after Immuno-Modulation by Androstenetriol." VCU Scholars Compass, 2005. http://hdl.handle.net/10156/2049.
Full text
22
Wendt, Emily Rose. "The role of CCL25 and CCR9 in intestinal inflammation." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:c8413dcb-4861-4afd-ae13-5cb88935e54d.
Full textAbstract:
Leukocyte extravasation is mediated in part by tissue specific chemotactic cytokines (chemokines) and specific chemokine receptors expressed on the surface of circulating cells. C-C chemokine ligand CCL25 is expressed exclusively in the intestine and thymus and mediates chemotaxis by cells expressing receptor CCR9. This chemokine and receptor pair may be relevant in the pathogenesis of intestinal inflammation, in diseases such as Crohn’s disease (CD) and coeliac disease. In this thesis I investigated CCR9 expression in situ, in tissues affected by intestinal inflammation, and also examined the effects of CCR9 antagonist treatment in patients. In vitro I investigated CCR9 function using human peripheral blood T cells enriched for CCR9 by cell sorting or all-trans retinoic acid treatment. Using tissues collected as part of a clinical trial in CD testing CCR9 antagonist, CCX282-B, I investigated ways of measuring if treatment reduced the number of CCR9 expressing cells in the intestinal mucosa. However, in situ staining for CCR9 by immunohistochemistry was unsuccessful, and in this thesis, I explored reasons why this might be the case. Treatment with CCX282-B did however, show a tendency to reduce T cell density in the intestinal mucosa, although results were highly variable between individuals. In an examination of human CCR9 function in vitro I demonstrate for the first time that CCL25 stimulates CCR9 surface internalization. These data clarify the observation that CCR9 staining by IHC produces poor results in tissues where ligand is abundant, such as the intestine and thymus. I describe a novel technique for measuring calcium flux in two populations simultaneously by flow cytometry, which confirmed that in a heterogeneous population of cells, only CCR9 expressing cells respond to CCL25 by calcium flux. Variability in clinical trials is partly created by the use of concomitant medications, and in CD, corticosteroids are widely used. For the first time I show that glucocorticoids (GC) impair CCR9 mediated chemotaxis, calcium flux and intracellular signalling without changes to CCR9 mRNA and surface protein expression. Reduced CCR9 mediated signalling was accompanied by an enhanced expression and function of co-expressed CXCR4, demonstrating that the effects of GC were receptor-specific and not mediated by non-specific toxicity or inhibition of cell signalling. In a second study CCX282-B was tested in patients with coeliac disease, and in this trial, there was no reported concomitant use of GCs. It was confirmed that dietary gluten stimulates significant T cell recruitment to the intestinal mucosa with a pronounced accumulation of intraepithelial lymphocytes (IEL) and a rise in the frequency of FoxP3 expressing cells. Patients on CCX282-B had lower IEL counts, and an equivalent proportion of FoxP3 expressing T cells, suggesting that CCR9 blockade restricted the recruitment of effector T cell subsets. This thesis confirms that the accumulation of T cells is central to inflammation in the intestine and that modulating chemokine receptor function may affect this. Furthermore, this thesis demonstrates that the function of CCR9 is suppressed by GCs, which are widely used therapeutically and therefore could identify a novel mechanistic basis for their activity in CD.
23
Kramer, Ryan M. "Molecular Signature Characterization of Select Agent Pathogen Progression." University of Cincinnati / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1394725717.
Full text
24
Burgoyne, Paul. "Improved dendritic cell therapy for cancer by enhancing in vivo lymph node migration using a novel chemokine-based sorting method." Thesis, University of Glasgow, 2019. http://theses.gla.ac.uk/39056/.
Full textAbstract:
Dendritic cells (DCs) are potent antigen presenting cells and are crucially involved in the induction of the adaptive immune response. Multiple DC subsets exist in the body at rest and during inflammation with unique tissue origins and development. The main function of DCs is the uptake of antigen from the peripheral tissue by endocytosis, and the transfer of this antigen to T cells within the lymph nodes (LNs) to generate an immune response against the antigen. Given the potency of the potential T cell response, DCs are an attractive cell type for therapeutic use in contexts such as cancer. Over 20 years of clinical trials have developed DCs for this purpose: although significant progress has been made, DC clinical trials still show subclinical and variable T cell responses in patients. Numerous strategies have been tested to improve this, including use of specific DC subsets, ex vivo activation and maturation of the cells using cytokines, different antigen loading strategies and different routes of injection. These, however, do not sufficiently take into consideration the migration capability of these injected cells, which severely limits the potential cell function. CCR7 is the chemokine receptor crucially involved in DC homing to LNs and is a marker of DC maturity, but it has been shown that ex vivo-generated cells do not consistently express this receptor. Using a novel sorting methodology to isolate DCs expressing CCR7, it is possible to improve the maturity and function of the injected cells, as well as in vivo migration. CCR7 expressing cells are more capable of generating mature T cell responses in vitro due to the expression of co-stimulatory molecules such as CD80 and CD86 and the production of T cell-attracting chemokines. The B16F10 mouse melanoma was used to assess the potential improvement in therapeutic DC use following CCR7-sorting. In the subcutaneous model after a single injection, or multiple prophylactic injections, of CCR7- sorted DCs there was significant control of the tumour growth and this resulted in a longer survival duration. This was attributed to the increased T cell response induced by DCs reaching the LN, as more antigen-specific T cells were present in the CCR7-expressing DC-receiving animals and that the T cell phenotype was more mature by surface marker expression. In the metastatic model, however, there was no difference in the overall tumour burden between groups despite having a significantly improved antigen-specific T cell response following injection of the CCR7-sorted DCs. Finally, it was shown that this CCR7-sorting methodology is directly translatable to clinical use using the clinical grade MACSQuant Tyto cell sorter, and that CCR7-sorted human monocyte-derived DCs were also more potent activators of T cells in vitro.
25
Abhyankar, Vrushali Pavan. "The chemokine and cytokine responses of a keratinocyte, dendritic cell, and T-cell co-culture model treated with P. gingivalis hemagglutinin B (HagB)." Thesis, University of Iowa, 2016. https://ir.uiowa.edu/etd/2033.
Full textAbstract:
Background
P. gingivalis, a non-motile, rod-shaped, anaerobic, Gram-negative bacterium is one of the principal sources of periodontal disease. It possesses a number of potential virulence factors thought to be important in the disease process including 5 hemagglutinins (Hag). One of these is HagB. It is a well characterized nonfimbrial adhesin expressed on the surface of P. gingivalis. HagB is very pro-inflammatory and induces robust chemokine and cytokine responses in vitro and in vivo. Since the chemokine and cytokine responses seen from single cells grown in tissue culture often are not representative of the chemokine and cytokine profiles seen in clinical samples or biopsy specimens, we devised a co-culture model of keratinocytes, dendritic cells, and T-cells to test the hypothesis that chemokine and cytokine responses from co-cultured cells would be more representative of responses seen in clinical samples from individuals with periodontal disease than single cell models.
Methods and materials
HagB was prepared by cloning hagb of P. gingivalis (1.4 kb) into the vector pQE31 (QIAGEN Inc., Valencia, CA); expressed in E. coli M15(pREP4)pQE31-TX1; and isolated from E. coli lysates by affinity chromatography using a Ni-charged resin (Profinity IMAC Resin, BioRad, Hercules, CA) and examined by SDS-PAGE. Co-culture models were treated with 10 µg/ml HagB (Test) or 10 µg/ml HagB diluent (Control). At 64 hours the supernatants were collected. Chemokine and cytokine biomarkers GM-CSF, CCL3 (MIP-1α), CCL4 (MIP-1β), CCL5 (RANTES), IL-1α, IL-6, IL-8, TNFα, IL-12(p40), and VEGF responses were determined using Milliplex immunoassays. HagB responses were corrected by subtracting the constitutive responses detected in supernatants incubated with HagB diluent. Statistical differences among groups were determined on Log10 transformed biomarker concentration using JMP 10 (version 10.0, SAS, CAR; NC).
Results
Buffers (e.g. HagB diluent) did not induce a chemokine or cytokine response, however there was a gradual increase in chemokine and cytokine responses from cells at 64 hours. These were subtracted from HagB induced responses. Responses generally fell in 2 groups; in one group containing VEGF, IL-12(p40), IL-6, RANTES and GM-CSF, there were no significant differences among groups (p>0.05). In another group containing IL-1α, IL-8, MIP-1α, MIP-1β and TNF-α, there were significant differences among groups (p< 0.05). Interestingly these resulting responses fell in 2 categories- GM-CSF, IL-12, IL-1α, IL-6 were less than 25pg/ml and IL-8, MIP-1α, MIP-1β, RANTES, TNFα and VEGF were more than 25pg/ml. Some responses were driven by a particular cell type e.g. GM-CSF produced by dendritic cells, RANTES produced by T- cells and VEGF produced by T cells. There were similar responses in HagB-induced IL-8, MIP-1β, MIP-1α and TNFα responses by dendritic cells + keratinocytes and dendritic cells + keratinocytes + T cells.
Conclusions
Co-culture models can more realistically produce chemokine and cytokine responses to agonists than individual cultures of cells, which is important for predicting and assessing novel therapeutic treatments of periodontal disease.
26
Benson, Bryan Lauck. "Mechanobiology of Leukocyte Adhesion." Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1537210425881461.
Full text
27
Lemma, S. (Siria). "Migration and adhesion associated molecules in lymphoma biology and their potential roles as biomarkers." Doctoral thesis, Oulun yliopisto, 2017. http://urn.fi/urn:isbn:9789526216041.
Full textAbstract:
Abstract Lymphomas are a heterogeneous group of malignancies that arise from lymphatic tissues. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma sub-type. It is an aggressive malignancy with an increasing incidence. The prognosis of DLBCL has improved significantly, but problems also remain. The clinical significance of central nervous system (CNS) relapses has become increasingly important. As secondary CNSL (sCNSL) and primary CNS lymphoma (PCNSL) are known to have poor prognoses; the prevention of sCNSL is of crucial importance. Peripheral T-cell lymphomas (PTCL) are rare neoplasms and include several lymphoma subtypes that possess complex and also overlapping morphological and immunophenotypic characteristics. The identification of different entities has improved, but the biological knowledge remains scarce when compared to DLBCL. The optimal treatment schemas for PTCLs are still lacking and they have long been treated with the same therapies as B-cell lymphomas, mainly with suboptimal treatment results. The aim of this study was to identify poor prognostic markers in DLBCL and PTCLs and potential biological markers for the prediction of DLBCL CNS relapse. The study material included patients with systemic DLBCL without CNS affision (sDLBCL), sCNSL, PCNSL and PTCLs. The expression of epithelial-mesenchymal transition (EMT) transcription factors (TFs), chemokines and their receptors and adhesion-, migration- and inflammatory responses-associated molecules were studied by means of immunohistochemistry. IEM was used to verify the specific subcellular location of the studied molecules. GEP was performed on 12 PTCL samples in order to compare the poor prognosis group with the good prognosis group and on one sDLBCL and one sCNSL sample from the time of primary diagnosis. The EMT TFs were found to be expressed in both DLBCL and PTCLs, where they ultimately proved to have prognostic relevance as well. In PTCLs, these TFs were able to delineate a disease group with a specific gene-expression profile. CXCR4, CXCR5, ITGA10, PTEN and CD44 were found to be differently expressed between DLBCL cases with CNS affision when compared to those without CNS disease. These molecules seem to play a role in the development of CNS relapse and hopefully, if further verified, will lead towards the identification of biological markers for CNS relapse predictionTiivistelmä Lymfoomat ovat heterogeeninen ryhmä imukudossyöpiä, joista diffuusi suurisoluinen B-solulymfooma (DLBCL) on yleisin alatyyppi. Se on aggressiivinen maligniteetti, jonka insidenssi on noussut viime vuosina. DLBCL potilaiden ennuste on parantunut merkittävästi, mutta yhä osa potilaista menehtyy tautiinsa. DLBCL:n keskushermostorelapsin kliininen merkitys on tänä päivänä aiempaa suurempi. Sekundaarisen keskushermostolymfooman (sCNSL) ja primaarin aivolymfooman (PCNSL) ennusteet ovat nykyhoidoilla huonoja, joten keskushermostorelapsin ennaltaehkäiseminen on tärkeää. Perifeeriset T-solulymfoomat (PTCLs) ovat ryhmä harvinaisia neoplasioita, joka sisältää useita eri alatyyppejä, joiden morfologiset ja immunofenotyyppiset ominaisuudet ovat monimuotoisia ja osin päällekkäisiä. Eri entiteettien indentifiointi on parantunut, mutta PTCL:ien biologinen tietämys on yhä DLBCL:aa heikompaa. PTCL:ien optimaalinen hoito ei ole selvillä ja tätä tautiryhmää on pitkään hoidettu samoilla hoidoilla kuin DLBCL:aa, mutta huonommilla hoitotuloksilla. Tutkimuksen tavoitteena oli löytää huonon ennusteen markkereita, joilla myös pystyttäisiin ennustamaan DLBCL:n keskushermostorelapsia. Aineisto koostui DLBCL, sCNSL, PCNSL ja PTCL näytteistä. Immunohistokemiallisilla värjäyksillä tutkittiin epiteliaalis-mesenkymaalisen transition (EMT) transkriptiotekijöitä (TF), kemokiinireseptoreita sekä adheesioon-, migraatioon ja inflammaatioon assosioituja molekyylejä. Immunoelektronimikroskopialla varmennettiin molekyylien lokalisaatio soluissa. Geeniekspressioprofiloinnilla (GEP) verrattiin kahdentoista hyvän ja huonon ennusteen ryhmään kuuluvan PTCL näytteen välisiä geeniekspressioeroja sekä kahden DLBCL potilaan näytteitä, joista toiselle kehittyi keskushermostorelapsi. EMT TF:ien ekspressiota nähtiin DLBCL ja PTCL näytteissä, joissa niillä myös todettiin olevan ennusteellista merkitystä. PTCL:ssa TF:t pystyivät erottelemaan tautiryhmän, jolla oli oma spesifinen geeniekspressioprofiilinsa. CXCR4, CXCR5, ITGA10, PTEN ja CD44 ekspressio oli erilaista systeemisissä DLBCL tapauksissa verrattuna sCNSL tapauksiin. Edellä mainituilla molekyyleillä näyttää olevan oma roolinsa keskushermostotaudin kehittymisessä ja jos nämä tulokset pystytään vahvistamaan tulevissa tutkimuksissa, johtavat ne toivottavasti kohti keskushermostorelapsiriskin tarkempaa tunnistamista
28
Teng, Kun-Yu Teng. "Molecular mechanisms underlying microRNA-122 mediated suppression of liver inflammation, fibrosis, and carcinogenesis." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1511206344798557.
Full text
29
White, Gemma. "The role of fractalkine (CX₃CL1) and its receptor (CX₃CR1) in vascular biology." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670108.
Full text
30
Cunningham, Crystal. "Expression of Chemokines and VEGFs in HNSCC." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1787.
Full textAbstract:
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. The 5-year survival rate when the cancer remains as a primary tumor is 81% but when it metastasizes to distant sites, defined as a metastatic cancer, it decreases dramatically to 26%. Approaches to prevent these cancers from undergoing these metastatic changes can greatly improve the survival and outcome of these cancer victims. This current study is examining the expression profiles of chemokines and VEGFs in HNSCC. By investigation the underlying pathways involved in the expressions of chemokines and VEGFS we hope to sort out the transcriptional regulation of these molecules. We used pharmological inhibitors of several important kinase pathways and the receptors involved in the transcription of chemokines and VEGFs. This study specifically looked at the proangiogenetic chemokines, CXCL5 and CXCL8, and their receptor CXCR2, and their possible impact on VEGFs, specifically VEGF-C and VEGF-A. From experimentation we concluded that HNSCC uses the MAPK pathway for regulation of the chemokines CXCL5 and CXCL8, but not for its downregulation. VEGF-A showed to be positively controlled by the MAPK pathway. The Akt pathway was found to downregulate VEGF-C, possibly from CXCR2. VEGF-C was not under control of the chemokines’ expression, VEGF-C and VEGF-A were also differentially regulated. The current study has begun to sort out the expression and regulation of chemokines and VEGFs in HNSCC. There are still many unanswered questions about the role these molecules play in HNSCC, but hopefully these conclusions will aid in finding improved treatments for patients diagnosed with head and neck cancer.
31
Madela-Mönchinger, Julia Cecilia. "The impact of rat cytomegalovirus gamma chemokine on dendritic cells." Doctoral thesis, Humboldt-Universität zu Berlin, 2021. http://dx.doi.org/10.18452/22863.
Full textAbstract:
Bis heute sind die beiden Ratten-Cytomegalovirus (RCMV)-Isolate RCMV-England (RCMV-E) und RCMV-Berlin (RCMV-B) die einzig bekannten Viren, die ein Homolog von XCL1 kodieren, einem g-Chemokin, das vom Virus kopiert wurde um das Chemokin-Netzwerk des Wirts zu beeinträchtigen. Wie das Wirtshomolog lockt vXCL1 ausschließlich dendritische Zellen (DC) an, die den XC-Chemokinrezeptor 1 (XCR1) exprimieren.
In dieser Arbeit wurde untersucht, inwieweit RCMV die XCL1-XCR1-Achse nutzt, um DC zu infizieren und sich im Wirt auszubreiten. In der Ratte konnten zwei DC-Hauptpopulationen identifiziert werden, XCR1+ CD4- und XCR1- CD4+ DC. Es konnte gezeigt werden, dass Überstände von RCMV-infizierten embryonalen Rattenfibroblasten ausschließlich die XCR1+ CD4- Population anlocken. Darüber hinaus konnte nachgewiesen werden, dass RCMV DC infiziert.
Durch die Anreicherung wurden DC aktiviert. Während der Infektion inhibierte RCMV die Hochregulation von Reifungsmarkern, einschließlich CD40, CD86 und CCR7. Unabhängig von vXCL1 scheint RCMV die DC-Funktionalität durch das Herunterregulieren von Reifungsgenen zu lähmen.
Um die Rolle von XCR1 und die Funktion von vXCL1 in vivo zu analysieren, wurden Xcr1+/+ und Xcr1-/- Ratten mit RCMV-B wt und RCMV-B D-vxcl1 infiziert. Während das XCR1- Expressionsniveau einen Einfluss auf die Geschwindigkeit der RCMV-Verbreitung in den Speicheldrüsen hatte, führte das Fehlen von vXCL1 zu einer starken Abnahme der Virusausbreitung. Die DC-Migration in die Speicheldrüsen war sowohl von vXCL1 als auch von XCR1 abhängig und war reduziert, wenn vXCL1 und XCR1 nicht vorhanden waren. Während der Infektion wurden CD8+ T-Zellen in die Speicheldrüsen rekrutiert. Diese Migration blieb jedoch aus, wenn Xcr1+/+ Ratten mit RCMV-B D-vxcl1 infiziert wurden.
Zusammenfassend besitzt RCMV die Fähigkeit DC unabhängig von der vXCL1-Expression zu infizieren. RCMV verwendet vXCL1, um XCR1+ DC anzulocken, was entscheidend für die Virusausbreitung in die Speicheldrüsen zu sein scheint.To date, the two Rat Cytomegalovirus (RCMV) isolates RCMV-England (RCMV-E) and RCMV-Berlin (RCMV-B) are the only known viruses that encode a homolog of XCL1, a gamma- chemokine adopted by viral piracy to interfere with the host’s chemokine network. Like its host homolog, vXCL1 exclusively attracts dendritic cells (DC) that express the XC chemokine receptor 1 (XCR1). In this work, it was investigated whether RCMV misuses the XCL1-XCR1 axis to infect DC in order to disseminate within the host. Initially, rat DC phenotyping revealed two major DC populations, XCR1+ CD4- DC and XCR1- CD4+. It could be shown that supernatants of RCMV-infected rat embryonic fibroblasts solely attracted the XCR1+ CD4- population. Moreover, RCMV was able to infect and replicate in DC. Due to digestion of the spleen and leukocyte enrichment DC became activated leading to full maturation 24 h after cell isolation. During infection, RCMV inhibited the upregulation of several maturation markers including CD40, CD86 and CCR7 and also led to reduced expression of MHCII, CD4 and XCR1. Regardless of vXCL1, RCMV appears to paralyze DC functionality by downregulating maturation genes. In order to analyze the role of XCR1 and vXCL1 function in vivo, Xcr1+/+ and Xcr1-/- rats were infected with RCMV-B wt and RCMV-B delta-vxcl1. Whereas the XCR1 expression level had an influence on the pace of RCMV-B wt dissemination to the salivary glands, the absence of vXCL1 led to a strong decrease in viral spread. DC migration to the salivary glands was dependent on vXCL1 as well as XCR1 and was markedly reduced when vXCL1 and XCR1 were not present. During infection, CD8+ T cells were recruited to the salivary glands, however, this migration was missing when Xcr1+/+ rats were infected with RCMV-B delta-vxcl1. In conclusion, RCMV has the ability to infect DC regardless of vXCL1 expression. RCMV uses vXCL1 to attract XCR1+ DC which appears to be important for viral dissemination to the salivary glands.
32
Ma, Manhong. "Chemokines and inflammation in wound healing following spinal cord contusion injury in the mouse /." The Ohio State University, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=osu1486462067843737.
Full text
33
Perpiñá, Viciano Cristina [Verfasser], Carsten [Gutachter] Hoffmann, Martin J. [Gutachter] Lohse, and Elke [Gutachter] Butt-Dörje. "Study of the activation mechanisms of the CXC chemokine receptor 4 (CXCR4) and the atypical chemokine receptor 3 (ACKR3) / Cristina Perpiñá Viciano ; Gutachter: Carsten Hoffmann, Martin J. Lohse, Elke Butt-Dörje." Würzburg : Universität Würzburg, 2020. http://d-nb.info/1222910365/34.
Full text
34
Laufer, Julia [Verfasser]. "Characterization of distinct chemokine receptor CCR7 signaling pathways : in health and disease / Julia Laufer." Konstanz : KOPS Universität Konstanz, 2018. http://d-nb.info/1206538953/34.
Full text
35
Zhou, Xuefei [Verfasser]. "Funktionelle Charakterisierung des C-Klasse Chemokins ATAC in vivo / Xuefei Zhou." Berlin : Freie Universität Berlin, 2010. http://d-nb.info/1024103714/34.
Full text
36
Smit, Flora [Verfasser]. "Cutaneous defense against Candida albicans: modulation of chemokine-driven anti-microbial immune responses / Flora Smit." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2018. http://d-nb.info/1172500274/34.
Full text
37
Mora, Ahmed. "Expression and function of the chemokine receptor XCR1 on murine CD8 + DC." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2010. http://dx.doi.org/10.18452/16088.
Full textAbstract:
In dieser Arbeit wurde die Expression von XCR1 in B6XCR1lacZ+/+ Reporter Mäusen charakterisiert, die β-Galaktosidase unter der Kontrolle des XCR1-Promotors exprimieren. In Gewebeschnitten konnten wir zeigen, dass eine starke XCR1-Expression nur in lymphatischen Organen wie Milz, Lymphknoten und Thymus nachweisbar ist. In der Milz fanden sich XCR1+ Zellen vor allem in der Marginal Zone, aber auch in der roten Pulpa und der T-Zell-Zone. Durchflusszytometrische Analysen zeigten, dass XCR1 in der Milz ausschließlich von dendritischen Zellen DZ exprimiert wird, hauptsächlich von der CD8+DZ Subpopulation aber auch von einer Minderheit der CD4−CD8−DZ. In vivo migrierten diese XCR1+ Zellen nach Applikation von chemotaktischen oder inflammatorischen Substanzen: Die Injektion sowohl einer ATAC-sezernierenden Zelllinie als auch von LPS lösten nach 3-9 h eine Translokation der XCR1+Zellen in die T-Zell-Zone der Milz aus. Untersuchungen der Phagozytose-Aktivität ergaben, dass nur XCR1+CD8+DZ, aber keine anderen DZ Subpopulationen, injizierte allogene Zellen aufnahmen, und dass eine Transfektion dieser Zellen mit ATAC diese Phagozytose signifikant verstärkte. Daher konnten wir allogene Zellen, die intrazellulär Ovalbumin OVA exprimierten, für die selektive Applikation von Antigen auf XCR1+DZ verwenden. Diese selektive Antigen-Applikation induzierte eine starke antigenspezifische zytotoxische Antwort von endogenen T-Zellen, ohne dass es zur Produktion von OVA-spezifischen Antikörpern kam. In Abwesenheit von ATAC war diese endogene zytotoxische Aktivität verringert. Durch adoptivem Transfer und Aktivierung von Wildtyp- oder ATAC-defizienten OVA-spezifischen transgenen CD8+TZellen konnten wir bestätigen, dass ATAC für die Erzeugung einer optimalen zytotoxischen Antwort benötigt wird. Die selektive Applikation von Antigen auf CD8+DZ stellt daher eine vielversprechende Strategie dar, um optimierte Vakzinierungs-Ansätze für die Auslösung einer zytotoxischen Immunantwort zu entwickelnThe G protein-coupled receptor XCR1 has been described as the sole receptor for the chemokine ATAC. As contradictory data were published on the expression pattern of XCR1, its role in the immune system has not yet been defined. In this work, expression of XCR1 was characterized in B6.XCR1 lacZ+/+ reporter mice which express β galactosidase under the control of the XCR1 promoter. In tissue sections, strong expression of XCR1 was only detected in lymphoid organs like spleen, lymph nodes and thymus. In the spleen, XCR1+ cells were mainly found in the marginal zones, but also in the red pulp and the T cell zones. Flow cytometric analysis demonstrated exclusive expression of XCR1 on DC, mainly on the CD8+ DC subset, but also on a minority of CD4− CD8− DC. In vivo, these XCR1+ cells migrated in response to chemotactic or inflammatory stimuli: application of either an ATAC-expressing cell line or LPS induced within 3 9 h the translocation of XCR1+ cells to the T cell area of the spleen. When tested for phagocytic capacity, XCR1+ CD8+ DC, but not other DC subsets, specifically took up injected allogeneic cells, and transfection of these cells with ATAC significantly enhanced their endocytosis by XCR1+ CD8+ DC. Thus, we could employ allogeneic cells expressing OVA intracellularly to target antigen selectively to XCR1+ DC. This antigen targeting induced a strong antigen-specific cytotoxic response by endogenous T cells without a generation of OVA-specific antibodies. In the absence of ATAC, the endogenous cytotoxic activity was markedly diminished. Adoptive transfer and activation of wild type or ATAC-deficient OVA-specific CD8+ transgenic T cells confirmed that ATAC is required for the generation of an optimal cytotoxic response. Targeting of antigen to CD8+ DC via XCR1 may thus be a promising strategy for the development of new vaccination approaches aimed at optimizing the induction of cytotoxic T cells.
38
Dau, Thérèse Thuy Dung. "Proteolytic modification of elastase and chemokine activities by neutrophil elastase and proteinase 3." Diss., Ludwig-Maximilians-Universität München, 2014. http://nbn-resolving.de/urn:nbn:de:bvb:19-185772.
Full text
39
Lachance, Claude. "Role of Fragile X-related protein 1 in controlling the expression of TNF and other pro-inflammatory cytokines and chemokines." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=32400.
Full textAbstract:
Tumor necrosis factor (TNF) is a key inflammatory cytokine that plays a major role in combating infections. Its dysregulation, however, can lead to uncontrolled inflammation which may cause deleterious conditions such as septic shock. Therefore, the expression of TNF is tightly regulated at both the transcriptional and post-transcriptional level. AU-rich elements, present in the 3'-untranslated region of TNF mRNA, are primarily known for their ability to stimulate rapid mRNA decay. ARE-binding proteins such as TTP and AUF-1 mediate this process. We have identified a new protein, Fragile X-related protein 1 (FXR1P), which binds to the ARE of TNF mRNA. The generation of a macrophage cell line, in which the Fxr1 gene is ablated, resulted in higher expression of TNF protein without affecting TNF mRNA steady state level or stability. Analysis of polysomes showed that TNF mRNA was associated preferentially with heavy polysome fractions in macrophages cell lines derived from FXR1P knockout mice, indicating a translational repressor role for FXR1P. We next defined the role of FXR1P in TNF induction by Toll-like receptor (TLR) ligands other than LPS (a TLR4 ligand). The effects of S28463, a synthetic TLR7 ligand, and CpG, a TLR9 ligand, were tested as they have potential clinical therapeutic properties. FXR1P ablation in macrophages did not alter TNF expression compared with wildtype macrophages stimulated with S28463. However, FXR1P-deficient macrophages stimulated with CpG had significantly higher TNF secretion than wildtype cells. Although CpG-stimulated FXR1P-KO cells had higher TNF mRNA steady state levels, no difference in TNF mRNA stability was observed compared with wilLe facteur onconécrosant de tumeur (TNF) est une cytokine inflammatoire qui joue un rôle important pour combattre diverses infections. La dérégulation de TNF peut cependant entraîner une inflammation non-contrôlée qui est à l'origine de diverses conditions pathologiques. L'expression de TNF est donc fortement régulé aux niveaux transcriptionnels et post-transcriptionnels. Les AREs (éléments riches en adénine\uridine) qui sont présents dans la région 3' non-traduite de l'ARNm de TNF sont reconnus pour leur capacité à stimuler rapidement la dégradation de ces ARNm. Plusieurs protéines se liant aux AREs ont la capacité de médier ce processus. Nous avons identifié une nouvelle protéine, FXR1P (Fragile X-related protein 1) capable de se lier à l'ARE de l'ARNm de TNF. L'utilisation d'une lignée cellulaire de type macrophage provenant de souris où le gène Fxr1 est inactivé a résulté en une expression plus élevée de la protéine TNF sans affecter les niveaux d'ARNm ni la stabilité de ceux-ci. L'analyse de polyribosomes a démontré que l'ARNm de TNF est associé de façon préférentielle avec les fractions lourdes des polyribosomes dans les macrophages FXR1-KO. Ceci indique un rôle de répression de la traduction de l'ARNm de TNF pour FXR1P. Nous avons par la suite définie le rôle de FXR1P lors de l'induction de TNF par les ligands de TLR (récepteur ressemblant à Toll) autres que LPS. Les effets de S28463 (TLR7-L) et de CpG (TLR9-L) ont été testé parce qu'ils possèdent des propriétés thérapeutiques potentielles. La stimulation avec S28463 n'a pas entrainé de différence d'expression de TNF entre les macrophages FXR1-KO et FXR1-WT.
40
Bird-Gordon, Kereen Suzetta. "Prostate Cancer Cells differentally express anti-inflmmatory and pro-inflammatory cytokines and chemokines: implications for prostate cancer immunotherapy." DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2007. http://digitalcommons.auctr.edu/dissertations/12.
Full textAbstract:
Anti-inflammatory specific cytokines and chemokines are elevated in many advanced tumors and correlate with poor prognosis. However, the differential expression of anti-inflammatory cytokines and chemokines in prostate cancer is not known. We investigated the hypotheses that androgen unresponsive DU145 and PC3 prostate cancer cells and androgen responsive LNCaP prostate cancer cells, differentially expressed selected anti-inflammatory and pro-inflammatory cytokines and chemokines and that, dendritic cells pulsed with prostate tumor antigens will induce mainly pro-inflammatory cytokines and chemokines in T cells using mouse models. Our results indicated that anti-inflammatory specific cytokines IL-1 0, IL-4, and anti-inflammatory specific chemokine CCL- 17 (TARC) and cognate receptor CCR4 are expressed in prostate cancer cell lines. Quantitative real-time PCR (qRT-PCR) revealed an almost five-fold increase in chemokine CCL17 and its cognate receptor CCR4 mRNA in androgen unresponsive DU145 and PC3 prostate cancer cell lines compared to androgen responsive prostate tumor LNCaP. Protein analysis indicated significantly increased secretion of anti-inflammatory cytokine IL- 10 by DU145 and PC3 compared to LNCaP. Furthermore, pro-inflammatory cytokine IFN-y and pro-inflammatory chemokine IP- 10 secretion were significantly less in these prostate cancer cells, when compared to immortalized normal prostate epithelial cells. Our in- vivo analysis revealed that T cells were activated by pulsed dendritic cells shown in the increase mRNA expression of pro-inflammatory cytokine IFN-y and pro-inflammatory chemokine IP- 10, and cognate receptor CXCR3. However, a predominant pro-inflammatory response was not observed as anti-inflammatory cytokines and chemokines were also seen. The production of anti-inflammatory cytokines and chemokines suggests a possible mechanism for prostate cancer to evade host immune responses by negatively modulating immune responses that are necessary for destroying cancers cells.. Cytokine and chemokine profiles could be used as potential prognostic markers for disease progression. Additionally, an effacious vaccine will depend on its ability to inhibit the recruitment of known distinct functional anti-inflammatory effector molecules, implicated in prostate cancer progression.
41
Madela-Mönchinger, Julia Cecilia [Verfasser]. "The impact of rat cytomegalovirus gamma chemokine on dendritic cells / Julia Cecilia Madela-Mönchinger." Berlin : Humboldt-Universität zu Berlin, 2021. http://d-nb.info/1233986139/34.
Full text
42
Sprague, Leslee W. "Dendritic Cell Culture With 2D and 3D Collagen Substrates." Ohio University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1311616312.
Full text
43
Schweneker, Marc [Verfasser]. "Identification and characterization of two novel proteins interacting with the chemokine- and HIV-1 co-receptor CCR5 / Marc Schweneker." Berlin : Freie Universität Berlin, 2017. http://d-nb.info/114004351X/34.
Full text
44
Hussein, Allami Risala [Verfasser]. "Influence of the chemokine CXCL12 on the progression and the signaling in colorectal cancer / Risala Hussein Allami." Mainz : Universitätsbibliothek Mainz, 2013. http://d-nb.info/1037459539/34.
Full text
45
Dau, Thérèse Thuy Dung [Verfasser], and Elisabeth [Akademischer Betreuer] Weiß. "Proteolytic modification of elastase and chemokine activities by neutrophil elastase and proteinase 3 / Thérèse Thuy Dung Dau. Betreuer: Elisabeth Weiß." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2014. http://d-nb.info/107545705X/34.
Full text
46
Thobe, Megan. "The Ron Receptor Tyrosine Kinase in Prostate Cancer." University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1273006729.
Full text
47
Abe, Philipp [Verfasser], Ralf [Gutachter] Stumm, Christoph Gutachter] Kaether, and Sandra [Gutachter] [Blaess. "Einfluss des Chemokins CXCL12 auf die Entwicklung neuronaler Strukturen / Philipp Abe ; Gutachter: Ralf Stumm, Christoph Kaether, Sandra Blaess." Jena : Friedrich-Schiller-Universität Jena, 2016. http://d-nb.info/1177613239/34.
Full text
48
Yester, Jessie. "Intra and extracellular functions of sphingosine-1-phosphate in sterile inflammation." VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/3245.
Full textAbstract:
Sterile inflammation is a key component of a variety of diseases including, gout, arthritis, type 1 diabetes, Alzheimer’s disease and multiple sclerosis (MS). Sterile inflammation induces the recruitment of immune cells via chemokines, such as CCL5 and CXCL10. Expression of these chemokines is dependent on IRF-1. Recently the FDA has approved the use of a pro-drug, FTY720 that after phosphorylation becomes a S1P mimetic for the treatment of MS. This report describes two novel and opposing mechanisms of S1P action in sterile inflammation. First, intracellular S1P acts as a cofactor of cIAP2 that inducesIL-1-dependent K63-polyubiquitination of IRF-1, which leads to the recruitment of immune cells to the site of inflammation. Conversely, extracellular S1P provides a feedback loop that inhibits CXCL10 and CCL5 expression through S1PR2 signaling. Accordingly, immune cell infiltration to sites of sterile inflammation is increased in S1PR2-/- production via calcium-dependent, but cAMP- and PKA-independent mechanisms that likely involve c-Fos expression and unconventional PKC activation. Elevated c-Fos could competitively inhibit CCL5 expression directly or indirectly via blocking IFN production. These two novel pathways highlight unexpected aspects of S1P signaling, and provide potential mechanisms that can be exploited for the improvement of therapeutics for the treatment of MS.
49
Natt, Jessica. "Plasmocytes et désordres immunitaires : impacts des chimiokines et de leurs récepteurs sur la biologie des cellules sécrétrices d’anticorps dans le syndrome WHIM et le lupus systémique." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS375.
Full textAbstract:
Les chimiokines (CK) et leurs récepteurs (RCK) régulent l’homéostasie leucocytaire et sont également des partenaires actifs dans la physiopathologie du syndrome WHIM et du lupus systémique (LS).Le syndrome WHIM est un déficit immuno-hématologique rare qui se caractérise notamment par une profonde lympho-neutropénie périphérique. Ce déficit est expliqué par un gain de fonction du RCK CXCR4, qui entraîne un défaut de désensibilisation du récepteur et une hyper-sensibilité à son ligand CXCL12. Malgré la lymphopénie caractéristique, les patients parviennent à générer une réponse immune humorale mais celle-ci n’est pas maintenue dans le temps. Afin de mieux comprendre la physiopathologie du syndrome WHIM, notre laboratoire a développé le modèle murin Cxcr4+/1013 qui présente une mutation gain de fonction de Cxcr4 similaire à celle observée chez certains patients. La première partie de ma thèse s’est intéressée à l’impact de ce gain de fonction de Cxcr4 sur la réponse immune. L’immunisation des souris Cxcr4+/1013 a permis de montrer que la désensibilisation de Cxcr4 limitait la différenciation des cellules productrices d’anticorps (Ac) appelées plasmocytes (PC). De plus, le gain de fonction de Cxcr4 est associé à une migration aberrante des PC et un défaut de leur maintien au long cours dans la moelle osseuse, pouvant ainsi expliquer la réponse vaccinale défectueuse observée chez les patients.La seconde partie de ma thèse a été consacrée à la caractérisation du profil migratoire des PC dans le LS. Le LS est une maladie auto-immune systémique, qui évolue par poussées et rémissions, et qui affecte plusieurs organes (peau, rein, système nerveux central…). L’initiation et l’exacerbation du LS sont médiées par les auto-Ac sécrétés par les PC autoréactifs. A ce jour, de par l’absence d’identification de marqueur spécifique de cette population, aucune thérapie ne parvient à cibler spécifiquement ces cellules. Une stratégie alternative consiste en la dérégulation de la domiciliation des PC autoréactifs dans les tissus enflammés, à l’origine même des dommages tissulaires. Ce projet s’est intéressé à l’identification du code migratoire des PC circulants de patients lupiques. J’ai cherché à savoir si les PC circulants de patients lupiques présentaient un profil d’expression de RCK distinct de ceux d’individus sains, pouvant ainsi expliquer le recrutement aberrant de ces cellules dans les tissus enflammés. Ces études ont été effectuées chez des patients en phases de poussée et de rémission mais également dans le modèle murin lupique NZB/W F1. Ces travaux suggèrent que les patients peuvent être stratifiés selon les RCK exprimés par les PC circulantsThe chemokines (CK) and their receptors (CKR) are essential for leukocyte homeostasis. They are also involved in the pathophysiology of several diseases including the WHIM syndrome and systemic lupus erythematosus (SLE).The WHIM syndrome is a rare immunodeficiency characterised by a severe peripheral lympho-neutropenia. It is caused by a gain-of-function of the CKR CXCR4, leading to a defect in desensitization of this receptor and a hyper-responsiveness to its ligand CXCL12. To better understand the pathophysiology of the WHIM syndrome, our laboratory developed the mouse model Cxcr4+/1013 harboring a natural mutation observed in some patients. Despite the lymphopenia, WHIM patients can mount a potent humoral immune response but that is not sustained over time. The maintenance of long-term antibody (Ab) titers is guaranteed by plasma cells (PCs) in the bone marrow (BM). The first part of my thesis was thus dedicated to the analysis of the role of a gain-of-function of Cxcr4 on PC differentiation and migration. The analysis of humoral response of Cxcr4+/1013 mice revealed a defect in the persistence of specific antibody titres in the absence of Cxcr4 desensitization. Furthermore, this was associated with an abnormal accumulation of a population of immature PCs in the BM.The second part of my work aimed to characterize the migratory potential of circulating PCs from SLE patients. SLE is a systemic autoimmune disease which can affect several organs like the skin, the kidneys or the central nervous system. SLE evolves in flare and remission phases and auto-Ab secreted by autoreactive PCs contribute to its pathophysiology and severity. Today, no specific treatment against autoreactive PCs exist. Targeting their migratory capacity to the inflamed tissues could be an alternative strategy. The objective of this project was to identify the migratory potential of SLE PCs. These studies were processed on samples from SLE patients during flare or remission, and on the lupus mouse model, the NZB/W F1 mice. We observed that the expression of different combinations of surface CKR may stratify several groups of SLE patients
50
Mehalick, Leslie Ann. "Sphingoid bases induce dose-dependent cytotoxicity and cytokine responses in human myeloid dendritic cells." Thesis, University of Iowa, 2013. https://ir.uiowa.edu/etd/2579.
Full textAbstract:
Sphingoid bases (sphingosine, dihydrosphingosine and phytosphingosine) have been recently found in the oral cavity where they may serve to fortify innate immunity against commensals and periodontal pathogens. In fact, sphingoid bases have potent antimicrobial activity against Gram- positive and Gram- negative bacteria including oral pathogens like Porphyromonas gingivalis. It is not known whether these lipids are cytotoxic or alter the chemokine and cytokine responses of human dendritic cells, a finding important to their future potential as a therapeutic for treatment of periodontal disease.
Objectives: The objective of this study was to determine the effects of sphingoid bases on the cytotoxicity and cytokine responses of human myeloid dendritic cells.
Methods: Dendritic cells were treated with sphingoid bases (0.2-80.0 μM) for 16 hours in the presence or absence of 0.02 μM hemagglutinin B, a nonfimbrial adhesin of P. gingivalis used as a pro-inflammatory stimulus. The cytotoxicity of the inocula and its ability to induce the production of chemokines and pro-inflammatory cytokines was determined after 16 hours.
Results: Higher concentrations of sphingoid bases were cytotoxic (e.g., 40.0-80.0 μM), but physiologic concentrations of sphingoid bases (e.g., 0.2-20.0 μM) were not. At 5, 10, or 20 μM, sphingosine did not enhance or attenuate any HagB-induced IL-8, GM-CSF, MIP-1α, MIP-1β, or TNFα response of human myeloid dendritic cells. At 5 or 10 μM, neither phytosphingosine nor dihydrosphingosine enhanced or attenuated any HagB- induced IL-8, GM-CSF, MIP-1α, MIP-1β, or TNFα response of human myeloid dendritic cells.
Conclusion: Sphingoid bases exhibit dose-dependent cytotoxicity and cytokine responses against human myeloid dendritic cells. But at physiologic concentrations sphingoid bases appear to be safe and efficacious at the doses needed to prevent or treat microbial infections in the oral cavity.