Disease relevance of CXCL10

• Ras-induced Modulation of CXCL10 and Its Receptor Splice Variant CXCR3-B in MDA-MB-435 and MCF-7 Cells: Relevance for the Development of Human Breast Cancer [1].
• IFN-alpha beta released by Mycobacterium tuberculosis-infected human dendritic cells induces the expression of CXCL10: selective recruitment of NK and activated T cells [2].
• Involvement of the interferon-gamma-induced T cell-attracting chemokines, interferon-gamma-inducible 10-kd protein (CXCL10) and monokine induced by interferon-gamma (CXCL9), in the salivary gland lesions of patients with Sjögren's syndrome [3].
• Serum concentrations of the interferon-gamma-inducible chemokine IP-10/CXCL10 are augmented in both newly diagnosed Type I diabetes mellitus patients and subjects at risk of developing the disease [4].
• Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation [5].

Psychiatry related information on CXCL10

• In the present study we identified a link between CXCL10 overexpression in the brain and human immunodeficiency virus dementia and demonstrated the presence of the chemokine CXCL10 and its receptor, CXCR3, in the neurons in the brains of macaques with simian human immunodeficiency virus encephalitis [6].
• Candidate gene analysis of IP-10 gene in patients with Alzheimer's disease [7].

High impact information on CXCL10

• In parallel, they show reduced expression of proinflammatory chemokines and cytokines, such as CXCL10, CCL2, and transforming growth factor-beta2, and of chondroitin sulfate proteoglycans participating in the formation of the glial scar [8].
• An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4 [9].
• In addition, higher potency and efficacy of I-TAC over IP-10 and HuMig is demonstrated by transient mobilization of intracellular calcium as well as chemotactic migration in both activated T cells and transfected cell lines expressing CXCR3 [10].
• IP-10 protein was detected in keratinocytes and the dermal infiltrate from active psoriatic plaques using an affinity-purified rabbit anti-IP-10 antibody in immunoperoxidase studies [11].
• Gene expression profiling revealed that the 3 oncogenes activate a common transcriptional program in thyroid cells that includes upregulation of the CXCL1 and CXCL10 chemokines, which in turn stimulate proliferation and invasion [12].

Chemical compound and disease context of CXCL10

• Here, we report a serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis (ON) treated with methylprednisolone, and 26 patients treated with placebo in two randomized controlled trials [13].
• Monocyte and lymphocyte targeting chemokines appear to play a role in caprine arthritis encephalitis (CCL2) and canine endotoxemia (CXCL10) [14].
• Elevation of serum CXCL9 and CXCL10 in ocular sarcoidosis correlated significantly with ocular disease activity and ACE (angiotensin converting enzyme) levels and was unrelated to the presence of BHL, erythrocyte sedimentation rate, white blood cell count, serum IgG, or serum lysozyme [15].
• Compared to the parental vector AdLuc, transduction with the RGD-deleted vector AdL.PB resulted in reduced CXCL10 activation despite increasing titers, implying that RGD-alpha(V) integrin interactions contribute to adenovirus induction of inflammatory genes [16].
• METHODS:: Serum levels of CXCL10 were measured in 22 patients with Graves' disease when hyperthyroid, when euthyroid under methimazole therapy, and 3 days after near-total thyroidectomy [17].
• Before 131I, mean CXCL10 was significantly higher in patients with GD and thyroiditis than controls or those with TNG [18].

Biological context of CXCL10

• Selective inhibition of CXCR3-B using siRNA resulted in an increase in CXCL10-mediated breast cancer cell proliferation through G(i) proteins and likely involving CXCR3-A [1].
• In cotransfection assays, using a full-length CXCL10 promoter-luciferase construct, we found that the activated form of Ras, Ha-Ras(12V), promoted CXCL10 transcriptional activation [1].
• These high affinity IP-10/CXCL10-specific receptors on epithelial cells may be involved in cell migration and, perhaps, in the spread of metastatic cells as they exit from the vasculature [19].
• Moreover, ECD histiocytes expressed interferon-gamma-inducible 10-kd protein (CXCL10), which is specifically induced by interferon-gamma, and interleukin-6 and RANKL, which are both implicated in bone remodeling [20].
• Several other chemokines in addition to CXCL10 were able to increase CCL22-mediated chemotaxis [21].

Anatomical context of CXCL10

• In this study, we have investigated the role of Ras activation in the regulation of CXCL10 and its receptor splice variant CXCR3-B in two human breast cancer cell lines MDA-MB-435 and MCF-7 [1].
• We have found that several nonhemopoietic cell types, including epithelial and endothelial cells, have abundant levels of a receptor that binds IP-10/CXCL10 with a Kd of 1-6 nM [19].
• A lymph node from an HIV-1-infected individual expressed CXCL10 and CXCL11 mRNAs in the paracortex, including venules, as detected by in situ hybridization, whereas neither mRNA was detected after highly active antiretroviral therapy [22].
• Treatment with a neutralizing anti-IP-10/CXCL10 antibody significantly reduced the number of infiltrating tubulointerstitial T cells without affecting monocyte migration and led to an improved renal function [23].
• In addition to its role in leukocyte migration, CXCL10 inhibits the angiogenic functions of the ELR-CXC chemokines as well as bFGF and VEGF [24].

Associations of CXCL10 with chemical compounds

• These results suggest that plasma concentrations of immunoreactive CXCL10 may be a predictor of responsiveness or nonresponsiveness to antiviral therapy with pegylated interferon (IFN) with or without ribavirin [25].
• IP-10/CXCL10 bursts, which were not observed in glatiramer acetate (GA)-treated patients, correlated with occurrence of flu-like symptoms [26].
• CXCL10-induced up-regulation of CXCR3 expression in the three cell lines was inhibited by cycloheximide, indicating that de novo protein synthesis is required for this process [27].
• The CSF concentration of CXCL10 was positively correlated with the CSF leukocyte count, the CSF concentration of neopterin, matrix metalloproteinase (MMP)-9, and intrathecal IgG and IgM synthesis [13].
• Of interest, intracellular [Ca(2+)] did not rise in response to I-TAC, IP-10, or Mig [28].

Physical interactions of CXCL10

• Complete deletion of the C-tail, including Hx8, resulted in an inactive phenotype that lacks CXCL8 binding sites and has an increased number of binding sites for CXCL10 [29].
• Chromatin imunoprecipitation combined with real-time PCR was used to check acetylation of histone H4 and recruitment of the STAT1 complex to the ISRE locus of the CXCL10 gene [30].

Regulatory relationships of CXCL10

• Furthermore, the presence of CCL5 and CXCL10 in the cytolytic granules of tissue-infiltrating CD8(+) T cells expressing CCR5 and CXCR3 reveals a potential self-recruiting mechanism involving activated effector cytotoxic T cells [31].
• CXCR3 expression was significantly induced by the overexpression of CXCL10 as determined by RT-PCR and FACS [32].
• Interestingly, the synthesis of CXCL10 was mainly dependent on the Mtb-induced production of IFN-alpha beta [2].
• CXCL10 production from cytomegalovirus-stimulated microglia is regulated by both human and viral interleukin-10 [33].
• Finally, adenosine augmented the release of the chemokine CCL17 and inhibited CXCL10 production by mDCs [34].

Other interactions of CXCL10

• Elevations in CXC ligand 9 (CXCL9), CXCL10, and CXCL11 were observed in all patients with HCV [25].
• Finally, we observed intense expression of CXCL10 and CXCR3 in association with human breast cancer in situ, indicating that these observations may be of pathophysiologic significance [1].
• The combination of CCL5 with CXCL10 but not the other chemokines markedly increased recruitment [35].
• Migration was subsequently inhibited by addition of neutralizing antibody to CCL4 and CXCL10 [36].
• Bacteria-induced CCL2, CCL7, CXCL9, and CXCL10 mRNA expression was partially dependent on ongoing protein synthesis [37].

Analytical, diagnostic and therapeutic context of CXCL10

• Ras significantly increased CXCL10 mRNA and protein expression as observed by real-time PCR, fluorescence-activated cell sorting analysis, and ELISA [1].
• The chemokine interferon (IFN)-gamma-inducible protein of 10 kDa (IP-10; CXCL10) has been implicated in recruitment of T cells into rejecting allografts yet appears ineffective at stimulating human peripheral blood CD4 T cells to transmigrate across tumor necrosis factor (TNF)-treated human endothelial cell (EC) monolayers in vitro [38].
• All examined chemokines and receptors could be detected in normal liver tissue and in AR biopsy specimens by RT-PCR and semiquantitative RT-PCR, demonstrating an overexpression of CXCL10 and -11 [39].
• As determined by immunohistochemistry, CXCL10 localized to epithelial cells at the site of infection [40].
• Furthermore, serum CCL17 and CXCL10 levels varied between AML patients and were determined by disease status (both chemokines) as well as patient age, chemotherapy and complicating infections (only CCL17) [41].

References