Disease relevance of CXCL9

• 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 [1].
• The CXC Chemokine MIG/CXCL9 Is Important in Innate Immunity against Streptococcus pyogenes [2].
• Increased serum concentrations of monokine induced by interferon-gamma/CXCL9 and interferon-gamma-inducible protein 10/CXCL-10 in Sydenham's chorea patients [3].
• A statistically significant increase of CXCL10/IP-10 and CXCL9/Mig expression, in thyroid tissue specimens obtained from subjects affected by Hashimoto's thyroiditis and recent onset Graves' disease has been reported [4].
• CONCLUSIONS: The results demonstrated that serum levels of CXCL9 and CXCL10 were elevated markedly in the patients with ocular sarcoidosis and correlated with ocular disease activity and ACE level [5].

Psychiatry related information on CXCL9

• CONCLUSIONS: TIG and MIG are effective measures for improving patient compliance in hypertension [6].

High impact information on CXCL9

• Finally, hrIL-12 strongly reduced the tumorigenicity of IL-12Rbeta2-transfected Burkitt lymphoma RAJI cells in SCID-NOD mice through antiproliferative and proapoptotic effects, coupled with neoangiogenesis inhibition related to human IFN-gamma-independent induction of hMig/CXCL9 [7].
• Lastly, fresh human IEL constitutively expressed CXCR-3 (the common receptor for IP-10 and MIG), and fresh IEL also exhibited chemotaxis to by rIP-10, rMIG, and epithelial-conditioned media [8].
• Production of IP-10 and MIG in fresh epithelial cells was supported by in situ hybridization and enzyme-linked immunosorbent assay [8].
• Variable numbers of pancreas-infiltrating T cells express MIG mRNA [9].
• The structure of human GzmA bound to a tripeptide CMK inhibitor, determined at a resolution of 2.4 A, reveals that the oligomeric state contributes to substrate selection by limiting access to the active site for potential macromolecular substrates and inhibitors [10].

Chemical compound and disease context of CXCL9

• 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 [5].
• In contrast, the CXC chemokines that lack the ELR motif, PF4, IP-10, and MIG, not only fail to induce significant in vitro endothelial cell chemotaxis or in vivo corneal neovascularization, but are found to be potent angiostatic factors in the presence of CXC chemokines containing the ELR motif [11].
• The effectiveness of a treatment combining gene therapy with plasmid-borne MIG (pORF-MIG) and low-dose cisplatin chemotherapy was determined using colon carcinoma (CT26) and Lewis lung carcinoma (LL/2c) murine models [12].
• Differentiation of the megakaryocytic leukemia cells, CMK, was induced by long-term (12 day) treatment with the combination of IL-3 and the nucleoside analogue ribavirin (RV), which reduces cellular GTP levels [13].
• We tested to what extent preincubation with the ribonucleotide reductase inhibitors fludarabine (F-ara-A) and hydroxyurea (HU) enhanced ara-CTP levels in two human myeloid (HL-60, CMK) and two lymphoblastic leukemia cell lines (MOLT-4, BLIN-1) and also in blasts from 28 children with acute leukemia (AML: 14, ALL: 14) [14].

Biological context of CXCL9

• CXCR3 was functional, inducing a rise in cytosolic-free Ca2+, actin reorganization, and chemotaxis in response to the CXC ligands CXCL9, -10, and -11 [15].
• CONCLUSION: We conclude, that despite a distinct up-regulation of CXCL9 mRNA in human hearts during cardiac allograft rejection, this was not reflected in the serum levels of the encoded protein [16].
• It is possible, however, that IP10 and MIG may locally influence Th1 cells via cell migration [17].
• Phylogenetic analyses of amino acid sequences revealed that SDF1 is the most divergent member and that the physically separated MIG-INP10 pair constitutes a distinct evolutionary lineage [18].
• From the gene expression profiling, CCR4, CCR3, MIG, CXCR3 and BLC were selected for immunohistochemistry [19].

Anatomical context of CXCL9

• Of note, maximal expression of IP-10/CXCL10 and Mig/CXCL9 was found in the thyroid gland of patients with recent-onset GD and was correlated with interferon (IFN)-gamma [20].
• TLR ligands and cytokines induce CXCR3 ligands in endothelial cells: enhanced CXCL9 in autoimmune arthritis [21].
• In lesions from this disease, MIG was detected in eosinophils by immunohistochemistry [22].
• Also in vitro, inflamed pharyngeal epithelium produced large amounts of MIG/CXCL9 in the presence of bacteria [2].
• Neutrophil collagenase degrades MIG into small fragments and cleaves IP-10 behind positions 71 and 73 [23].

Associations of CXCL9 with chemical compounds

• In asthmatic patients, the ex vivo release of IP-10 and MIG was attenuated in PBMC activated with allergen, mitogens and IL-18 (p < 0.05) [24].
• METHODS: The spontaneous and TNF-alpha-stimulated secretion of IL-1beta, IL-8, IP-10 and MIG from HT-29 and Caco-2 cells was tested with, or without pretreatment with allicin [25].
• The program was carried out via intramuscular delivery of pORF-MIG at 100 mug/mouse twice a week for 4 weeks, and/or intraperitoneal delivery of cisplatin at 0.6 mg/kg/mouse every 3 days for 48 days [12].
• Outside-In signaling of soluble and solid-phase fibrinogen through integrin alphaIIbbeta3 is different and cooperative with each other in a megakaryoblastic leukemia cell line, CMK [26].
• This report identifies cDNA for a structurally altered P(2X1)-like receptor in megakaryocytic cell lines (Dami and CMK 11-5) and platelets that, when transfected into nonresponsive 1321 cells, confers a specific sensitivity to ADP with the pharmacologic rank order of ADP > > ATP > > > alpha,beta-methylene-ATP as measured by Ca(++) influx [27].

Regulatory relationships of CXCL9

• This supports the notion that CXCL9 interaction with cells expressing CXCR3 has an important role in the recruitment of mononuclear cells, a pivotal event in the pathogenesis of acute lung allograft rejection [28].
• In contrast, inhibition of the constitutive NF-kappaB in HSC-2 cells by adenovirus-mediated gene transfer of a dominant-negative IkappaBalpha suppressed the IFNgamma-induced expression of the CXCL9 and CXCL10 mRNAs [29].
• We conclude that MIG production correlates significantly with enhanced T-cell IFN-gamma production induced by M. tuberculosis-specific antigens ESAT-6/CFP-10 [30].

Other interactions of CXCL9

• Elevations in CXC ligand 9 (CXCL9), CXCL10, and CXCL11 were observed in all patients with HCV [31].
• Levels of CXCL10 and CXCL9 decreased following successful antiviral therapy; CXCL11 did not decline significantly during or in the first 6 months after therapy [31].
• Systemic CXCL9 levels decreased from pre- to grass pollen season in allergics (P < 0.05), whereas CCL17 decreased in non-allergics (P < 0.05) over the same period [32].
• Gelatinase B degrades IP-10 and cleaves MIG at three different sites in its extended carboxyterminal region [23].
• Levels of TARC, MDC, and MIG were significantly decreased after treatment when the skin lesions disappeared in these patients [33].

Analytical, diagnostic and therapeutic context of CXCL9

• In this study, we demonstrate that CXCL9 and CXCL10 are up-regulated in unique patterns following tracheal transplantation in mice [34].
• Quantitative real-time PCR confirmed these findings and revealed up-regulated mRNA levels of another chemoattractant that activates CXCR3, monokine induced by IFN-gamma (Mig; CXCL9) [35].
• Prediction of acute renal allograft rejection by urinary monokine induced by IFN-gamma (MIG) [36].
• In pH-adjusted urine, MIG and IP-10 were determined by modified ELISA [36].
• MIG values indicated both imminent rejection and response to successful antirejection therapy [36].

References