Disease relevance of Cxcl10

• Neutralization of IFN-inducible protein 10/CXCL10 exacerbates experimental autoimmune encephalomyelitis [1].
• The chemokines (CXCL9, CXCL10 and CXCL11) and associated CXCR3 receptor are expressed during the inflammatory process from multiple sclerosis, atherosclerosis or organ transplantation resulting in the recruitment of lymphocytes leading to tissue damage [2].
• Hypothermia upregulated the transcripts of several genes, including, chemokine ligands CCL2, CXCL2, CXCL10, and CCL20, and interleukins IL-1alpha, IL-1beta, and IL-6 [3].
• In conclusion, this present study shows that 2 CXC-chemokines, GRO/KC and IP10/mob-1, are produced by testicular somatic cells of seminiferous tubules, strongly indicating a likely role of these chemokines in the accumulation of neutrophils and T lymphocytes during orchitis of various origins [4].
• Two chemokines, interferon inducible protein 10 and monocyte chemotactic protein 3, were fused to lymphoma Ig variable regions (sFv) [5].

High impact information on Cxcl10

• Northern analysis indicated that mRNAs for mob-1 and another chemokine, mcp-1, were induced after cerulein hyperstimulation in vivo. mob-1 mRNA was also induced by retrograde injection of bile salts and by cerulein in acinar cells in vitro. mob-1 protein was localized to exocrine cells in pancreata of diseased animals [6].
• Immunopathological and chemokine analysis during the acute phase revealed that there were marked macrophage infiltration with myocyte necrosis and up-regulation of MCP-1 and IFN-gamma-inducible protein-10 (IP-10) [7].
• IFN-gamma-inducible protein 10 (IP-10) is a CXC chemokine that stimulates the directional migration of activated T cells, particularly Th1 cells [8].
• Administration of plasmid DNA encoding self IP-10 was found capable of breaking down immunological tolerance to IP-10, resulting in the generation of self-specific immunity to the gene product of the vaccine [8].
• We show here that during the course of adjuvant-induced arthritis the immune system mounts a notable Ab titer against self-IP-10 [9].

Chemical compound and disease context of Cxcl10

• Chronic intrathecal infusion of phosphorothioate or phosphodiester antisense oligonucleotides against cytokine responsive gene-2/IP-10 in experimental allergic encephalomyelitis of lewis rat [10].

Biological context of Cxcl10

• Interferon-inducible protein-10 involves vascular smooth muscle cell migration, proliferation, and inflammatory response [11].
• The effects of CXCL10 were not accompanied by a shift in resting membrane potential (RMP) or input resistance [12].
• In this paper, four classes of natural product inhibitors (IC50 ranging 0.1-41 microM) have been described that block the CXCR3 receptor interaction of IP-10 ligand [2].
• The kinetics of GRO/KC and IP-10/mob-1 mRNA expression by peritubular and Sertoli cells (significant stimulation as early as 1 hour and 4 hours post-exposure to the stimuli, respectively) are compatible with the hypothesis of a rapid mobilisation of these cells in an inflammatory process [4].
• GRO/KC (growth-related oncogene) and IP-10/mob-1 (IFN-gamma-inducible protein) are two CXC-chemokines which attract neutrophils and activated T lymphocytes, respectively, have been studied for their ability to participate to testicular inflammation (orchitis) [4].

Anatomical context of Cxcl10

• These results suggest that the early increased CXC-chemokine expression, such as IP-10 and MIG, which has been known to be mainly produced by macrophages, may play a critical role in the stronger cellular xenograft rejection compared with allograft rejection [13].
• The observation that interferon-inducible protein-10 (IP-10) is up-regulated in ethanol-treated fetal brain may indicate the presence of a disease process recruiting CD8+ T-cells capable of interfering with myelination [14].
• IP-10 induced a concentration-dependent stimulation of DNA synthesis, cell proliferation, and cell migration of rat aortic smooth muscle cells [11].
• Furthermore, IP-10 mRNA expression was induced in the rat carotid artery after balloon angioplasty [11].
• IFN-gamma-inducible protein 10 (IP-10) is a CXC chemokine that is thought to manifest a proinflammatory role because it stimulates the directional migration of activated T cells, particularly Th1 cells [9].

Associations of Cxcl10 with chemical compounds

• Differential display identifies neuroendocrine-specific protein-A (NSP-A) and interferon-inducible protein 10 (IP-10) as ethanol-responsive genes in the fetal rat brain [14].
• Using mRNA differential display, we isolated a rat homologue to murine and human IP-10 from lipopolysaccharide-stimulated carotid arteries [11].
• To explore further the potential role of IP-10 in focal stroke, we demonstrated a dose-dependent chemotactic action of IP-10 on C6 glial cells and enhanced attachment of rat cerebellar granule neurons [15].
• Ang II and TNF-alpha induced the expression of IP-10 (1.5 and 3.4-fold) and MCP-1 (2.4 and 4-fold) in VSMC [16].
• Therefore, two groups of fasting rats injected IP with physiological saline, and another two groups given IP 10 mg/kg CGP 39551 and 0.5 mg/kg MK-801 received 15 IU/kg crystalline zinc insulin IP [17].

Regulatory relationships of Cxcl10

• These findings suggest that CXCL10 produced in the LN plays a specific inhibitory role in the development of Th1-mediated diseases such as EAE by holding sensitized and activated Th1s expressing CXCR3 in the draining LN [1].

Other interactions of Cxcl10

• However, we observed that neutralization of IP-10 increased IFN-gamma protein in bronchoalveolar lavage (BAL) fluid of F344 rats 7 days after inoculation compared with rats that received normal rabbit serum [18].
• Expression of the CXCR3 chemokine receptor supports a direct effect of CXCL10 on hippocampal neurons [12].
• In this study, we provide evidence for direct modulatory effects of the chemokine, CXCL10, on the physiology of hippocampal neurons maintained in primary culture [12].
• The culture supernatant of cells transfected with these DNAs inhibited the migration of T cells and macrophages induced by MCP-1 and IP-10 [7].
• IL-8 and MIP-2 levels in the ischemic hemispheres peaked at 24 h, whereas IP-10 showed a biphasic profile with two peaks at 6 h and 6 days after pMCAO [19].

Analytical, diagnostic and therapeutic context of Cxcl10

• CONCLUSION: Overall, these results suggest that the more aggressive rejection of xenografts compared with allografts is due to the earlier expression of CXC-chemokines, IP-10 and MIG, and subsequent adjuvant effects of proinflammatory cytokines [13].
• Increased IFN-gamma protein in bronchoalveolar lavage fluid of anti-IP-10 antibody-treated F344 rats following Sendai viral infection [18].
• The double staining immunofluorescence study clearly demonstrated that the elevated expression of IP-10 was mostly detected in the podocyte and very partly in mesangial area [20].
• In the present work, using Northern blot and immunocytochemistry, we aimed to investigate whether GRO/KC and IP-10/mob-1 are produced within the seminiferous tubules of the testis and if these chemokines are induced by a number of pro-inflammatory cytokines and lipopolysaccharides (LPS) [4].
• CONCLUSION: Our study suggests a possible role of IP-10 and RANTES in acute rejection and early monitoring of chemokines may be helpful in predicting the outcome of pancreas transplantation [21].

References