Disease relevance of Cxcl10

• In addition, IP-10(-/-) mice exhibited an impaired contact hypersensitivity response, characterized by decreased ear swelling and reduced inflammatory cell infiltrates [1].
• T Cell Antiviral Effector Function Is Not Dependent on CXCL10 Following Murine Coronavirus Infection [2].
• Both CXCR3 and CXCL10/IFN-inducible protein 10 are required for resistance to primary infection by dengue virus [3].
• Furthermore, IP-10(-/-) mice infected with a neurotropic mouse hepatitis virus had an impaired ability to control viral replication in the brain [1].
• CONCLUSION: We prepared a novel potent IP-10 antagonist and demonstrated its ability to ameliorate the progression of autoimmune sialadenitis [4].

Psychiatry related information on Cxcl10

• Herein, we evaluated the contributions of CXC chemokine ligand 10 (CXCL10) in promoting innate defense mechanisms following coronavirus infection of the CNS [5].

High impact information on Cxcl10

• IP-10 is critical for effector T cell trafficking and host survival in Toxoplasma gondii infection [6].
• Here, we found that the F4/80-positive macrophages in DNase II(-/-) fetal liver specifically produce a set of cytokines such as IFNbeta, TNFalpha, and CXCL10 [7].
• Hepatic LN DCs preferentially produced CXCL10 to attract 5'-bromo-2'-deoxyuridine (BrdU)+CD4+ T cells and form clusters with IFN-gamma-producing CD4+ T cells by day 7 after antigen challenge [8].
• Thus, mature DC-derived CXCL10 is pivotal to retain Th1 lymphocytes within T cell areas of draining LNs and optimize the Th1-mediated immune responses [8].
• Pivotal role of dendritic cell-derived CXCL10 in the retention of T helper cell 1 lymphocytes in secondary lymph nodes [8].

Chemical compound and disease context of Cxcl10

• Type 1 diabetes is considered to be a Th1-dominant autoimmune disease, and a suppressive effect of CXCL10 neutralization on diabetes development has been reported in a cyclophosphamide-induced accelerated diabetes model through induction of beta cell proliferation [9].
• We found that IP-10 is highly expressed in a mouse model of pulmonary fibrosis induced by bleomycin [10].
• To determine whether PPARgamma ligands reduce this inflammation in part by reducing TH1 chemoattractant levels in vivo, the TZD pioglitazone was tested for its effects on a TH1 chemokine (CXCL10) in 2 models of colitis (i.e., dextran sodium sulfate and 2,4,6-dinitrobenzene sulfonic acid-mediated colitis) [11].
• A series of the C7-substituted A-ring pyrrole derivatives of duocarmycin were synthesized, and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice [12].

Biological context of Cxcl10

• RESULTS: IP-10 analogs truncated by 5 or more amino acid residues from the N-terminal failed to induce chemotaxis and calcium influx by CXCR3-expressing cells [4].
• Our data demonstrated that IP-10 was not required for the trafficking of pathogenic T cells into the CNS in EAE but played an unexpected role in determining the threshold of disease susceptibility in the periphery [13].
• We have examined the tissue distribution of 10-kd inflammatory protein (IP-10) mRNA expression in C57Bl/6 mice injected intravenously (i.v.) with various inflammatory stimuli [14].
• 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 [15].
• Transcription factor IRF-1 mediates cytokine-induced islet dysfunction, apoptosis, and iNOS gene expression but down-regulates IP-10 gene expression [16].

Anatomical context of Cxcl10

• Initial IP-10 production was localized to endothelial cells, and only IP-10 was induced by isografting [17].
• Compared with IP-10(+/+) donors, use of IP-10(-/-) donors reduced intragraft expression of cytokines, chemokines and their receptors, and associated leukocyte infiltration and graft injury [17].
• Immunological analysis revealed that IP-10(-/-) mice had impaired T cell responses [1].
• We found a marked synergy between HA and IFN-gamma on Mig and IP-10 mRNA and protein expression in mouse macrophages [18].
• Blocking of IP-10, but not monokine induced by IFN-gamma, aborts severity of Ag-specific injury of pancreatic beta cells and abrogates type 1 diabetes [19].

Associations of Cxcl10 with chemical compounds

• Indeed, the Trif-dependent gene cxcl10 was not expressed in ECs after LPS stimulation [20].
• First, LPS-induced IP-10 mRNA expression was blocked in cells cotreated with cycloheximide [21].
• Our experiments demonstrate that IP-10 is up-regulated in the lung after allergen challenge [22].
• Crg-2 expression was noted in vivo in multiple models of hepatic and bile duct injury, including bile duct ligation and CCl(4), D-galactosamine, and methylene dianiline toxic liver injuries [23].
• In contrast, IVAG administration of R-848 resulted in high levels of plasma IP-10, similar to those seen after parenteral administration, but overall, weaker or shorter-lived local immune responses than obtained with CpG ODN [24].

Physical interactions of Cxcl10

• The inhibitory effect of CXCL10/IP-10 on the binding of dengue virus to cells may represent a novel contribution of this chemokine to the host defense against viral infection [25].
• TNF-alpha at doses up to 10 ng/ml and soluble immune complexes up to 150 micrograms/ml antibody evoked 3- to 5-fold increases in IP-10 mRNA expression, much less than the 30- to 70-fold increases seen with IFN-gamma and LPS [26].

Regulatory relationships of Cxcl10

• IP-10 mRNA was strongly induced by interferon-gamma (IFN-gamma) in liver and kidney but only poorly in skin, heart, and lung [14].
• Xenografts showed stronger interferon (IFN)-inducible 10-kDa protein (IP-10) and monokine induced by IFN (MIG) mRNA expression levels, which appeared earlier than in the allografts [27].
• Interferon regulatory factor-1 down-regulates cytokine-induced IP-10 expression in pancreatic islets [16].
• Interleukin-10 suppresses IP-10 gene transcription by inhibiting the production of class I interferon [21].
• However, analysis of the susceptibility of CXCL10-deficient mice to lymphocytic choriomeningitis virus-induced meningitis revealed that these mice just like CXCR3-deficient mice were partially resistant to this disease, whereas wild-type mice invariably died [28].
• We show that the increased IRF-3 and IFN-beta-induced STAT1 activation are responsible for the autocrine IFN-beta-dependent preferential production of IP-10 by regulatory DCs [29].

Other interactions of Cxcl10

• The in vivo neutralization of either Mig or IP-10 significantly reduced the severity of IPS compared with control-treated animals, and an additive effect was observed when both ligands were blocked simultaneously [30].
• MCP-1, IP-10, and MIP-2 RNA expression significantly correlated with clinical score [31].
• Chemokine CXCL10 (IP-10) is sufficient to trigger an immune response to injected antigens in a mouse model [32].
• TNFR1-/- mice with EAE had significantly higher expression of CXCL10 mRNA (but not CCL5 mRNA) in the CNS compared to WT mice with EAE [33].
• RESULTS: Cytokine-treated WT islets demonstrated an increase in IRF-1 and iNOS gene expression, inhibition of GSIR, increased rates of apoptosis, and increased gene transcription and protein release for IP-10 and MCP-1 [16].

Analytical, diagnostic and therapeutic context of Cxcl10

• Donor-derived IP-10 initiates development of acute allograft rejection [17].
• These data emphasize the pivotal role of donor-derived IP-10 in initiating alloresponses, with implications for tissue engineering to decrease immunogenicity, and demonstrate that chemokine redundancy may not be operative in vivo [17].
• In the present study, we report that targeted deletion of IP-10 did not diminish the expression, severity, or histopathology of EAE induced by active immunization with 100 micro g of myelin oligodendrocyte glycoprotein peptide (MOG)p35-55 [13].
• Analysis of IP-10 mRNA distribution in the liver and kidney by in situ hybridization indicated that expression in both tissues was most prominent in the reticuloendothelial cell system, particularly in the endothelial lining of the microvascular circulation [14].
• Induction of Crg-2 was also examined following two-thirds hepatectomy, a model that minimally injures the remaining liver, but that requires a large hepatic regenerative response [23].

References