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Articles de revues sur le sujet "Interferon Gamma-Induced Protein 10 CXCL1"
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Gautam, Aarti, Saurabh Dixit, Mario T. Philipp, Shree R. Singh, Lisa A. Morici, Deepak Kaushal et Vida A. Dennis. « Interleukin-10 Alters Effector Functions of Multiple Genes Induced by Borrelia burgdorferi in Macrophages To Regulate Lyme Disease Inflammation ». Infection and Immunity 79, no 12 (26 septembre 2011) : 4876–92. http://dx.doi.org/10.1128/iai.05451-11.
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ABSTRACTInterleukin-10 (IL-10) modulates inflammatory responses elicitedin vitroandin vivobyBorrelia burgdorferi, the Lyme disease spirochete. How IL-10 modulates these inflammatory responses still remains elusive. We hypothesize that IL-10 inhibits effector functions of multiple genes induced byB. burgdorferiin macrophages to control concomitantly elicited inflammation. Because macrophages are essential in the initiation of inflammation, we used mouse J774 macrophages and liveB. burgdorferispirochetes as the model target cell and stimulant, respectively. First, we employed transcriptome profiling to identify genes that were induced by stimulation of cells with live spirochetes and that were perturbed by addition of IL-10 to spirochete cultures. Spirochetes significantly induced upregulation of 347 genes at both the 4-h and 24-h time points. IL-10 inhibited the expression levels, respectively, of 53 and 65 of the 4-h and 24-h genes, and potentiated, respectively, at 4 h and 24 h, 65 and 50 genes. Prominent among the novel identified IL-10-inhibited genes also validated by quantitative real-time PCR (qRT-PCR) were Toll-like receptor 1 (TLR1), TLR2, IRAK3, TRAF1, IRG1, PTGS2, MMP9, IFI44, IFIT1, and CD40. Proteome analysis using a multiplex enzyme-linked immunosorbent assay (ELISA) revealed the IL-10 modulation/and or potentiation of RANTES/CCL5, macrophage inflammatory protein 2 (MIP-2)/CXCL2, IP-10/CXCL10, MIP-1α/CCL3, granulocyte colony-stimulating factor (G-CSF)/CSF3, CXCL1, CXCL5, CCL2, CCL4, IL-6, tumor necrosis factor alpha (TNF-α), IL-1α, IL-1β, gamma interferon (IFN-γ), and IL-9. Similar results were obtained using sonicated spirochetes or lipoprotein as stimulants. Our data show that IL-10 alters effectors induced byB. burgdorferiin macrophages to control concomitantly elicited inflammatory responses. Moreover, for the first time, this study provides global insight into potential mechanisms used by IL-10 to control Lyme disease inflammation.
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Sakamoto, Shinichi, Hidenori Takahashi, Xue Tan, Yuji Inoue, Yoko Nomura, Yusuke Arai, Yujiro Fujino, Hidetoshi Kawashima et Yasuo Yanagi. « Changes in multiple cytokine concentrations in the aqueous humour of neovascular age-related macular degeneration after 2 months of ranibizumab therapy ». British Journal of Ophthalmology 102, no 4 (1 août 2017) : 448–54. http://dx.doi.org/10.1136/bjophthalmol-2017-310284.
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PurposeTo determine changes in multiple cytokine concentrations in the anterior chamber during the induction phase of ranibizumab treatment in patients with neovascular age-related macular degeneration (AMD).MethodsThis prospective study included 48 treatment-naïve neovascular AMD eyes of 48 patients who received three consecutive monthly injections of ranibizumab at the Japan Community Health Care Organization Tokyo Shinjuku Medical Center between November 2010 and August 2012. We collected ~0.2 mL aqueous humour before the first and third (2 months later) injections. Controls were 80 eyes with cataracts without retinal disease. The cytokines C-X-C motif chemokine ligand 1 (CXCL1), interferon-γ-induced protein 10 (IP-10), C-X-C motif chemokine ligand 12 (CXCL12), C-X-C motif chemokine ligand 13 (CXCL13), monocyte chemoattractant protein 1 (MCP-1), CCL11, C-C motif chemokine ligand 11 (CCL11), interleukin-6 (IL-6), interleukin-10 (IL-10) and matrix metalloproteinase 9 (MMP-9) were analysed using multiplex cytokine assays.ResultsMean ages of the patients with AMD and controls were 73 and 75 years, respectively, and 31 (65%) and 37 (46%) subjects were men, respectively. Polypoidal choroidal vasculopathy was found in 27 eyes (56%). Mean concentrations of cytokines in aqueous humour in patients with neovascular AMD before the first and third ranibizumab injections were as follows (in pg/mL): CXCL1, 8.4 and 3.3; IP-10, 110 and 55; CXCL12, 480 and 240; CXCL13, 9.2 and 2.6; MCP-1, 620 and 220; CCL11, 7.1 and 2.8; IL-6, 5.9 and 1.6; IL-10, 0.15 and 0.015 (all p<0.0001), and MMP-9, 0.92 and 1.5 (p=0.0216), respectively. Concentrations of all cytokines decreased significantly after two consecutive ranibizumab injections, except for MMP-9, which increased significantly.ConclusionsAfter two monthly consecutive antivascular endothelial growth factor injections, inflammatory cytokine levels in the aqueous humour of the eyes with AMD were strongly suppressed, while MMP-9 levels increased.
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Colvin, Richard A., Gabriele S. V. Campanella, Lindsay A. Manice et Andrew D. Luster. « CXCR3 Requires Tyrosine Sulfation for Ligand Binding and a Second Extracellular Loop Arginine Residue for Ligand-Induced Chemotaxis ». Molecular and Cellular Biology 26, no 15 (1 août 2006) : 5838–49. http://dx.doi.org/10.1128/mcb.00556-06.
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ABSTRACT CXCR3 is a G-protein-coupled seven-transmembrane domain chemokine receptor that plays an important role in effector T-cell and NK cell trafficking. Three gamma interferon-inducible chemokines activate CXCR3: CXCL9 (Mig), CXCL10 (IP-10), and CXCL11 (I-TAC). Here, we identify extracellular domains of CXCR3 that are required for ligand binding and activation. We found that CXCR3 is sulfated on its N terminus and that sulfation is required for binding and activation by all three ligands. We also found that the proximal 16 amino acid residues of the N terminus are required for CXCL10 and CXCL11 binding and activation but not CXCL9 activation. In addition, we found that residue R216 in the second extracellular loop is required for CXCR3-mediated chemotaxis and calcium mobilization but is not required for ligand binding or ligand-induced CXCR3 internalization. Finally, charged residues in the extracellular loops contribute to the receptor-ligand interaction. These findings demonstrate that chemokine activation of CXCR3 involves both high-affinity ligand-binding interactions with negatively charged residues in the extracellular domains of CXCR3 and a lower-affinity receptor-activating interaction in the second extracellular loop. This lower-affinity interaction is necessary to induce chemotaxis but not ligand-induced CXCR3 internalization, further suggesting that different domains of CXCR3 mediate distinct functions.
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Tribouillard-Tanvier, Déborah, James F. Striebel, Karin E. Peterson et Bruce Chesebro. « Analysis of Protein Levels of 24 Cytokines in Scrapie Agent-Infected Brain and Glial Cell Cultures from Mice Differing in Prion Protein Expression Levels ». Journal of Virology 83, no 21 (26 août 2009) : 11244–53. http://dx.doi.org/10.1128/jvi.01413-09.
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ABSTRACT Activation of microglia and astroglia is seen in many neurodegenerative diseases including prion diseases. Activated glial cells produce cytokines as a protective response against certain pathogens and as part of the host inflammatory response to brain damage. In addition, cytokines might also exacerbate tissue damage initiated by other processes. In the present work using multiplex assays to analyze protein levels of 24 cytokines in scrapie agent-infected C57BL/10 mouse brains, we observed elevation of CCL2, CCL5, CXCL1, CXCL10, granulocyte-macrophage colony-stimulating factor (GM-CSF), gamma interferon (IFN-γ), interleukin 1α (IL-1α), IL-1β, IL-6, and IL-12p40. Scrapie agent-infected wild-type mice and transgenic mice expressing anchorless prion protein (PrP) had similar cytokine responses in spite of extensive differences in neuropathology. Therefore, these responses may be primarily a reaction to brain damage induced by prion infection rather than specific inducers of a particular type of pathology. To study the roles of astroglia and microglia in these cytokine responses, primary glial cultures were exposed to scrapie agent-infected brain homogenates. Microglia produced only IL-12p40 and CXCL10, whereas astroglia produced these cytokines plus CCL2, CCL3, CCL5, CXCL1, G-CSF, IL-1β, IL-6, IL-12p70, and IL-13. Glial cytokine responses from wild-type mice and transgenic mice expressing anchorless PrP differed only slightly, but glia from PrP-null mice produced only IL-12p40, indicating that PrP expression was required for scrapie agent induction of other cytokines detected. The difference in cytokine response between microglia and astroglia correlated with 20-fold-higher levels of PrP expression in astroglia versus microglia, suggesting that high-level PrP expression on astroglia might be important for induction of certain cytokines.
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Zeng, Xianying, Thomas A. Moore, Michael W. Newstead, Jane C. Deng, Steven L. Kunkel, Andrew D. Luster et Theodore J. Standiford. « Interferon-Inducible Protein 10, but Not Monokine Induced by Gamma Interferon, Promotes Protective Type 1 Immunity in Murine Klebsiella pneumoniae Pneumonia ». Infection and Immunity 73, no 12 (décembre 2005) : 8226–36. http://dx.doi.org/10.1128/iai.73.12.8226-8236.2005.
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ABSTRACT CXC chemokines that lack the ELR motif, including interferon-inducible protein 10 [IP-10 (CXCL10)] and monokine induced by gamma interferon (IFN-γ) [MIG (CXCL9)], have been shown to mediate the generation of type 1 immune responses. In this study, we found that intrapulmonary administration of the gram-negative bacterium Klebsiella pneumoniae resulted in the local and systemic expression of IP-10, followed sequentially by MIG expression. MIG mRNA expression in the lungs of Klebsiella-infected mice required the endogenous production of IFN-γ, whereas IP-10 was expressed in both an IFN-γ-dependent and an IFN-γ-independent fashion. Antibody-mediated neutralization of IP-10 resulted in reduced bacterial clearance and decreased survival, whereas bacterial clearance was unaltered in mice treated with anti-MIG antibody. Impaired bacterial clearance in anti-IP-10 antibody-treated mice was associated with significant reductions in the number and/or activational status of NK and NK-T cells, CD4+ T cells, and γδ T cells, as well as a reduction in the expression of IFN-γ. Conversely, the transient transgenic expression of murine IP-10 using adenovirus-mediated gene transfer resulted in improved bacterial clearance when IP-10 adenovirus was given concomitant with intrapulmonary bacterial challenge. These results indicate that IP-10 is an important component of innate immunity against extracellular bacterial pathogens of the lung and may represent a candidate molecule for immunotherapy in the setting of severe respiratory tract infection.
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Hameed, Ruaa Salim. « Upregulated CXCL10 gene Expression in SARS-CoV-2 Infected people ». BASRA JOURNAL OF SCIENCE 40, no 2 (1 septembre 2022) : 357–65. http://dx.doi.org/10.29072/basjs.20220208.
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Interferon and interferon-induced genes play a crucial role in early-stage post-infection virus defense. C-X-C10, also known as interferon gamma-induced protein 10 or small-inducible cytokine B10, is encoded by the CXCL10 gene and is essential for T-helper cell recruitment. The purpose of this study was to assess the gene expression of CXCL10 in SARS-CoV-2-positive and -negative individuals using qPCR. The results demonstrated a 35-fold increase in CXCL10 expression in SARS-CoV-2-positive individuals vs to negative samples. In conclusion, the elevated gene expression of CXCL10 in SARS-CoV-2 patients is a signal for the immune system to respond to the invading virus and may be taken into account in the design of future vaccines.
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Asensio, Valérie C., Joachim Maier, Richard Milner, Kaan Boztug, Carrie Kincaid, Maxime Moulard, Curtis Phillipson et al. « Interferon-Independent, Human Immunodeficiency Virus Type 1 gp120-Mediated Induction of CXCL10/IP-10 Gene Expression by Astrocytes In Vivo and In Vitro ». Journal of Virology 75, no 15 (1 août 2001) : 7067–77. http://dx.doi.org/10.1128/jvi.75.15.7067-7077.2001.
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ABSTRACT The CXC chemokine gamma interferon (IFN-γ)-inducible protein CXCL10/IP-10 is markedly elevated in cerebrospinal fluid and brain of individuals infected with human immunodeficiency virus type 1 (HIV-1) and is implicated in the pathogenesis of HIV-associated dementia (HAD). To explore the possible role of CXCL10/IP-10 in HAD, we examined the expression of this and other chemokines in the central nervous system (CNS) of transgenic mice with astrocyte-targeted expression of HIV gp120 under the control of the glial fibrillary acidic protein (GFAP) promoter, a murine model for HIV-1 encephalopathy. Compared with wild-type controls, CNS expression of the CC chemokine gene CCL2/MCP-1 and the CXC chemokine genes CXCL10/IP-10 and CXCL9/Mig was induced in the GFAP-HIV gp120 mice. CXCL10/IP-10 RNA expression was increased most and overlapped the expression of the transgene-encoded HIV gp120 gene. Astrocytes and to a lesser extent microglia were identified as the major cellular sites for CXCL10/IP-10 gene expression. There was no detectable expression of any class of IFN or their responsive genes. In astrocyte cultures, soluble recombinant HIV gp120 protein was capable of directly inducing CXCL10/IP-10 gene expression a process that was independent of STAT1. These findings highlight a novel IFN- and STAT1-independent mechanism for the regulation of CXCL10/IP-10 expression and directly link expression of HIV gp120 to the induction of CXCL10/IP-10 that is found in HIV infection of the CNS. Finally, one function of IP-10 expression may be the recruitment of leukocytes to the CNS, since the brain of GFAP-HIV gp120 mice had increased numbers of CD3+ T cells that were found in close proximity to sites of CXCL10/IP-10 RNA expression.
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Smit, Martine J., Dennis Verzijl, Paola Casarosa, Marjon Navis, Henk Timmerman et Rob Leurs. « Kaposi's Sarcoma-Associated Herpesvirus-Encoded G Protein-Coupled Receptor ORF74 Constitutively Activates p44/p42 MAPK and Akt via Gi and Phospholipase C-Dependent Signaling Pathways ». Journal of Virology 76, no 4 (15 février 2002) : 1744–52. http://dx.doi.org/10.1128/jvi.76.4.1744-1752.2002.
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ABSTRACT The G protein-coupled receptor encoded by Kaposi's sarcoma-associated herpesvirus, also referred to as ORF74, has been shown to stimulate oncogenic and angiogenic signaling pathways in a constitutively active manner. The biochemical routes linking ORF74 to these signaling pathways are poorly defined. In this study, we show that ORF74 constitutively activates p44/p42 mitogen-activated protein kinase (MAPK) and Akt via Gi- and phospholipase C (PLC)-mediated signaling pathways. Activation of Akt by ORF74 appears to be phosphatidylinositol 3-kinase (PI3-K) dependent but, interestingly, is also mediated by activation of protein kinase C (PKC) and p44/p42 MAPK. ORF74 may signal to Akt via p44/p42 MAPK, which can be activated by Gi, through activation of PI3-K or through PKC via the PLC pathway. Signaling of ORF74 to these proliferative and antiapoptotic signaling pathways can be further modulated positively by growth-related oncogene (GROα/CXCL1) and negatively by human gamma interferon-inducible protein 10 (IP-10/CXCL10), thus acting as an agonist and an inverse agonist, respectively. Despite the ability of the cytomegalovirus-encoded chemokine receptor US28 to constitutively activate PLC, this receptor does not increase phosphorylation of p44/p42 MAPK or Akt in COS-7 cells. Hence, ORF74 appears to signal through a larger diversity of G proteins than US28, allowing it to couple to proliferative and antiapoptotic signaling pathways. ORF74 can therefore be envisioned as an attractive target for novel treatment of Kaposi's sarcoma.
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Widney, Daniel P., Yan Hu, Amy K. Foreman-Wykert, Kim C. Bui, Tam T. Nguyen, Bao Lu, Craig Gerard, Jeff F. Miller et Jeffrey B. Smith. « CXCR3 and Its Ligands Participate in the Host Response to Bordetella bronchiseptica Infection of the Mouse Respiratory Tract but Are Not Required for Clearance of Bacteria from the Lung ». Infection and Immunity 73, no 1 (janvier 2005) : 485–93. http://dx.doi.org/10.1128/iai.73.1.485-493.2005.
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ABSTRACT Intranasal inoculation of mice with Bordetella bronchiseptica produces a transient pneumonia that is cleared over several weeks in a process known to require both neutrophils and lymphocytes. In this study, we evaluated the roles of the chemokines MIG (CXCL9), IP-10 (CXCL10), and I-TAC (CXCL11) and their common receptor, CXCR3. Following bacterial inoculation, message expression of interleukin-1 (IL-1), IL-6, and the neutrophil-attracting chemokines KC, LIX, and MIP-2 was rapidly induced, with maximal expression found at 6 h. In contrast, message expression of gamma interferon, MIG, IP-10, and I-TAC peaked at 2 days. Expression of all of these chemokines and cytokines returned to near baseline by 5 days, despite the persistence of high levels of live bacteria at this time. Induced MIG, IP-10, and I-TAC protein expression was localized in areas of inflammation at 2 to 3 days and was temporally associated with increased levels of CXCR3+ lymphocytes in bronchoalveolar lavage fluid. There was no increase in mortality in mice lacking CXCR3. However, the clearance of bacteria from the lung and trachea was delayed, and the recruitment of lymphocytes and NK cells was slightly decreased, for CXCR3−/− mice relative to CXCR3+/+ mice. We conclude that the CXCR3 receptor-ligand system contributes to pulmonary host defense in B. bronchiseptica infection by recruiting lymphocytes and NK cells into the lung.
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Cheeran, Maxim C. J., Shuxian Hu, Wen S. Sheng, Phillip K. Peterson et James R. Lokensgard. « CXCL10 Production from Cytomegalovirus-Stimulated Microglia Is Regulated by both Human and Viral Interleukin-10 ». Journal of Virology 77, no 8 (15 avril 2003) : 4502–15. http://dx.doi.org/10.1128/jvi.77.8.4502-4515.2003.
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ABSTRACT Glial cells orchestrate immunocyte recruitment to focal areas of viral infection within the brain and synchronize immune cell functions through a regulated network of cytokines and chemokines. Since recruitment of T lymphocytes plays a critical role in resolving cytomegalovirus (CMV) infection, we investigated the production of a T-cell chemoattractant, CXCL10 (gamma interferon-inducible protein 10) in response to viral infection of human glial cells. Infection with CMV was found to elicit the production of CXCL10 from primary microglial cells but not from astrocytes. This CXCL10 expression was not dependent on secondary protein synthesis but did require the phosphorylation of p38 mitogen-activated protein (MAP) kinase. In addition, migration of activated lymphocytes toward supernatants from CMV-stimulated microglial cells was partially suppressed by anti-CXCL10 antibodies. Since regulation of central nervous system inflammation is essential to allow viral clearance without immunopathology, microglial cells were then treated with anti-inflammatory cytokines. CMV-induced CXCL10 production from microglial cells was suppressed following treatment with interleukin-10 (IL-10) and IL-4 but not following treatment with transforming growth factor β. The IL-10-mediated inhibition of CXCL10 production was associated with decreased CMV-induced NF-κB activation but not decreased p38 MAP kinase phosphorylation. Finally, CMV infection of fully permissive astrocytes resulted in mRNA expression for the viral homologue to human IL-10 (i.e., cmvIL-10 [UL111a]) in its spliced form and conditioned medium from CMV-infected astrocytes inhibited virus-induced CXCL10 production from microglial cells through the IL-10 receptor. These findings present yet another mechanism through which CMV may subvert host immune responses.
Thèses sur le sujet "Interferon Gamma-Induced Protein 10 CXCL1"
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Geng, Wei, et 耿瑋. « The role of interferon-gamma inducible protein 10 (IP10) in early-phase graft injury induced late-phase cisplatin resistance after livertransplantation ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B50162731.
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Background:
Hepatocellular carcinoma is one of the most fatal diseases worldwide. Liver transplantation dramatically improved the survival rate of HCC patients. However, tumor recurrence remains a huge threat to HCC patients without any promising curative treatment. Chemotherapy, as one of the potential treatments to recurrent HCC, did not show any significant effect either.
Objective:
We aim to investigate the role of interferon-gamma inducible protein 10 (IP10) in acute-phase liver graft injury induced late-phase cisplatin resistance after liver transplantation and to explore the underlying mechanism. Furthermore, a potential adjuvant therapy was expected to be identified to sensitize cisplatin treatment in HCC.
Materials and methods:
A rat orthotopic liver transplantation model was established with applying whole or small-for-size (50%) graft. Afterwards, a rat hepatoma cell (MH7777) was injected via portal vein to generate recurrent tumor. The expressions of genes linked to multi-drug resistance and graft injury were compared between tumors developed after liver transplantation using small and whole grafts. IP10 expression was further validated in clinical samples from two cohorts of patients including HCC patients with hepatectomy and HCC patients with liver transplantation. The extracellular and intracellular roles of IP10 were examined in vitro by using IP10 recombinant protein and IP10 stable transfectants in HCC cell lines. The correlation between IP10 expression and tumor growth was investigated in three in vivo nude mice models including a subcutaneous model, an orthotopic model and ischemia reperfusion injury model. The underlying mechanism was further explored in vitro, in vivo and in clinical samples. IP10 neutralizing antibody was employed as an adjuvant therapy to identify its effect on sensitizing cisplatin treatment in HCC.
Results:
The expressions of multidrug resistant genes were significantly up-regulated in liver and tumor from small-for-size group in rat liver transplantation model. IP10 was selected as the potential target for its constantly higher expression in liver and tumor tissues in small-for-size group. In clinical studies, IP10 was overexpressed in around 45% HCC patients with hepatectomy. The expression of circulating IP10 well correlated with tumor recurrence and small graft ratio in HCC patients after liver transplantation. In in vitro studies, it was demonstrated that overexpression of IP10 could significantly promote HCC cell proliferation either in short term or in long term cisplatin administration. In in vivo studies, subcutaneous and orthotopic nude mice models showed that the overexpression of IP10 have significant correlations with larger tumor volume and less tumor necrosis after cisplatin treatment. In mechanism studies, IP10 overexpression was found to be well correlated with the activation of endoplasmic reticulum (ER) stress signaling pathways in vitro and further validated in vivo models and in clinical specimens. IP10 neutralizing antibody was identified as a potential therapy which could sensitize cisplatin treatment in vitro and in vivo.
Conclusions:
The high expression of IP10 was identified in two cohorts of clinical samples and showed significant correlations with tumor recurrence. Graft injury induced IP10 overexpression could significantly increase cisplatin resistance after liver transplantation via ER stress signaling pathways. IP10 neutralizing antibody may be applied as an alternative treatment for recurrent HCC after liver transplantation.published_or_final_version
Surgery
Doctoral
Doctor of Philosophy
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LOCATELLI, LUIGI. « Expression of aVB6 integrin by Pkhd1-defective cholangiocytes links enhanced ductal secretion of Macrophage chemokines to progressive portal fibrosis in Congenital Hepatic Fibrosis ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2013. http://hdl.handle.net/10281/41733.
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BACKGROUND AND AIMS: Congenital Hepatic Fibrosis (CHF) is caused by mutations in PKHD1, a gene encoding for fibrocystin, a protein of unknown function, expressed in cholangiocyte cilia and centromers. In CHF, biliary dysgenesis is accompanied by severe progressive portal fibrosis and portal hypertension. The mechanisms responsible for portal fibrosis in CHF are unclear. The αvβ6 integrin mediates local activation of TGFβ1 and is expressed by reactive cholangiocytes during cholestasis. To understand the mechanisms of fibrosis in CHF we studied the expression of αvβ6 integrin and its regulation in Pkhd1del4/del4 mice.
METHODS: In Pkhd1del4/del4 mice we studied, at different ages (1-12 months): a) portal fibrosis (Sirius Red) and portal hypertension (spleen weight/body weight); b) αvβ6 mRNA and protein expression (RT-PCR, IHC); c) α-SMA and TGFβ1 mRNA expression (RT-PCR); d) portal inflammatory infiltrate (IHC for CD45 and FACS analysis of whole liver infiltrate); f) cytokines secretion from cultured monolayers of primary cholangiocytes (Luminex assay); g) cytokine effects on monocyte/macrophage proliferation (MTS assay) and migration (Boyden chamber); h) TGFβ1 and TNFα effects on β6 integrin mRNA expression by cultured cholangiocytes before and after inhibition of the TGFβ receptor type II (TGFβRII); i) TGFβ1 effects on collagen type I (COLL1) mRNA expression by cultured cholangiocytes.
RESULTS: Pkhd1del4/del4 mice showed a progressive increase in αvβ6 integrin expression on biliary cyst epithelia. Expression of αvβ6 correlated with portal fibrosis (r=0.94, p<0.02) and with enrichment of a CD45+ve cell infiltrate in the portal space (r=0.97, p<0.01). Gene expression of TGFβ1 showed a similar age-dependent increase. FACS analysis showed that 50-75% of the CD45+ve cells were macrophages (CD45/CD11b/F4/80+ve). Cultured polarized Pkhd1del4/del4 cholangiocytes secreted from the basolateral side significantly increased amounts of CXCL1 and CXCL10 (p<0.05). Both cytokines were able to stimulate macrophage migration (p<0.05). Basal expression of β6 mRNA by cultured Pkhd1del4/del4 cholangiocytes (0.015±0.002 2^-dCt) was potently stimulated by the macrophage-derived cytokines TGFβ1 (0.017±0.002 2^-dCt, p<0.05) and TNFα (0.018±0.003 2^-dCt, p<0.05). Inhibition of TGFβRII completely blunted TGFβ1 (0.014±0.003 2^-dCt, p<0.05) but not TNFα effects (0.017±0.001 2^-dCt, p=ns) on β6 mRNA. COLL1 mRNA expression by cultured Pkhd1del4/del4 cholangiocytes (0.0009±0.0003 2^-dCt) was further and significantly increased after TGFβ1 stimulation (0.002±0.0005 2^-dCt, p<0.05).
CONCLUSIONS: Pkhd1del4/del4 cholangiocytes possess increased basolateral secretory functions of chemokines (CXCL1, CXCL10) able to orchestrate macrophage homing to the peribiliary microenvironment. In turn, by releasing TGFβ1 and TNFα, macrophages up-regulate αvβ6 integrin in Pkhd1del4/del4 cholangiocytes. αvβ6 integrin activates latent TGFβ1, further increasing the fibrogenic properties of cholangiocytes.
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Huang, Mei-Liang, et 黃美椋. « Analysis of human interferon-gamma-inducible protein 10 (IP-10)/CXCL10 promoter polymorphism at position -938 ». Thesis, 2007. http://ndltd.ncl.edu.tw/handle/95334133739233112603.
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博士臺灣大學
流行病學研究所
95
Introduction - Interferon-γ inducible protein 10 (IP-10)/CXCLl10 was shown to be an indicator of disease progress for severe acute respiratory syndrome (SARS); a high plasma level in the early clinical stage was associated with subsequent adverse outcome. The mechanism that triggers CXCL10 expression in SARS-CoV infection is still unknown. Method - We conducted a genetic epidemiological study to identify the single nucleotide polymorphism (SNP) of CXCL10 that might be associated with severe SARS clinical outcomes. With luciferase assay and electromobility shift assay (EMSA), we conducted in vitro functional study of the polymorphic alleles of CXCL10 promoter with the attempt to identify the regulatory factors for CXCL10 expression. Results - Five SNPs of CXCL10 were typed for 108 SARS patients along with 242 healthy control DNAs. A genotype TT at the CXCL10(-938) SNP locus was identified to correlate with severity of SARS-CoV infected patients, especially among SARS patients with a detectably higher nasopharyngeal virus load. DNA fragment of the 996 bp upstream of the CXCL10 start codon containing either (-938C) or (-938T) SNP was cloned into the luciferase reporter pGL3 vector along with a series of 5’ end truncated CXCL10 promoter DNA fragments. With IFN-γ stimulation in A549 cell and HMEC-1 cells, the shortest two fragments (-704, and -413) showed a high luciferase activity, which dropped with each increment of the 5’ end DNA length; stimulation with IFN-γ and TNF-α in combination induced a higher luciferase activity, but the drop of activity was reversed with the fragment of -704 and -996, suggesting possibly IFN-γ associated negative regulation factors and TNF-α associated positive regulation factors could bind to this region. The difference of luciferase activity between the two alleles of CXCL10(-996C) and CXCL10(-996T) could not be consistently demonstrated, however. We used nuclear extracts from IFN-γ induced THP-1 cells and the 32P-labeled probes of CXCL10(-928~-948) promoter sequence containing (-938C) or (-938T) and antibodies against a number of TFs antibodies to perform EMSA. The (-938C) probe consistently binds to more nuclear proteins than the (-938T) probe, and three putative binding proteins, YY-1, MZF and Pax-6, of CXCL10 (-938) were found to reduce the shifted band in EMSA and supershift assay. The activation functions of YY-1 and MZF on CXCL10 expression were demonstrated by luciferase assay and the results showed YY-1 and MZF could trigger the activation of CXCL10, however, YY-1 and MZF induced activity were not different between the two alleles. Conclusion - The genotype TT of CXCL10 (-938) SNP was associated with adverse outcome of SARS patient. The DNA sequence flanking the CXCL10 (-938) SNP locus possibly contain binding motifs of YY-1, MZF and Pax-6. However, the functional difference between these two alleles of CXCL10 (-938) could not be demonstrated in vitro by luciferase assay and EMSA in the study.
Actes de conférences sur le sujet "Interferon Gamma-Induced Protein 10 CXCL1"
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Bai, Xiyuan, Kathryn Chmura, Alida Ovrutsky, Russell P. Bowler, Robert Scheinman, Rebecca E. Oberley-Deegan, Shaobin Shang, Diane Ordway et Edward D. Chan. « Mycobacterium Tuberculosis Increases Interferon-Gamma Inducible Protein-10 (Ip-10) And Monokine Induced By Interferon-Gamma (MIG) Protein Despite Inhibition Of Ip-10 And Mig Gene Transcription ». Dans American Thoracic Society 2011 International Conference, May 13-18, 2011 • Denver Colorado. American Thoracic Society, 2011. http://dx.doi.org/10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a3344.
Texte intégral
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Chen, C. T., S. Park, M. Bhargava et P. A. Torzilli. « Inhibitory Effect of Mechanical Load on IL-1 Induced Cartilage Degradation Is Mediated by Interferon-Gamma and IL-1 Receptor 1 ». Dans ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-193230.
Texte intégralRésumé :
Matrix remodeling in articular cartilage is regulated by the elevation and activation of aggrecanases (ADAMTS-4 and ADAMTS-5) and matrix metalloproteinases (MMPs) [2–4, 7–9, 10]. Several recent studies from our and other groups have shown that mechanical loading can counteract interleukin 1 (IL-1) induced pro-inflammatory and catabolic events by down-regulating aggrecanases, MMPs, and pro-inflammatory genes [1, 3, 5, 6], but the molecular mechanism is not clear. Many previous studies have shown that the regulation of pro-inflammatory effect of IL-1 come from several aspects: anti-inflammatory cytokines (TGF-β, IL-10, IL-6 and interferon γ), IL-1 receptor related proteins (IL-1R1, IL-1R2, and IL-1Ra) as well as a family of intracellular inhibitory protein called Suppressor Of Cytokine Signaling (SOCS.) SOCS1 and SOCS3 are especially important, since they can inhibit both MAPK and NF-κB pathways induced by IL-1 [12]. The objective of this study was to determine whether mechanical load affected anti-inflammatory mediators along with anti-catabolic events.