Disease relevance of Cxcl9

• 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 [1].
• Collectively, these results suggest that in the sensitized host, CXCR3, IP-10, and Mig are required for optimal DTH responsiveness but are not essential for containing HSV-1 replication in the ear pinna [2].
• Immunohistochemistry confirmed that PTLD tissues contain less IL-18 and Mig protein than tissues with infectious mononucleosis [3].
• Surprisingly, there was no expression in the lungs of mice infected with vaccinia, unlike the elevated expression shown previously for other interferon-regulated chemokines, such as Crg2 and Mig [4].
• In the present study, murine Mig RNA was found to be expressed at higher levels in regressing Burkitt's lymphoma tumors established in nude mice compared with progressively growing tumors [5].

High impact information on Cxcl9

• HEVs did not express detectable levels of MCP-1; however, a subset of HEVs in inflamed lymph nodes in wild-type (but not tumor necrosis factor [TNF] null mice) expressed MIG and this subset of HEVs preferentially supported monocyte binding [6].
• The transferred CTLs produce neither chemokine; rather, they activate (via the secretion of IFN-gamma) hepatocytes and nonparenchymal cells of the liver to produce (Crg2)IP-10 and Mig [7].
• Expression of CXCR3, the receptor for MIG, was detected on a small subset of peripheral blood monocytes and on a significant percentage of recruited monocytes [6].
• Tumor necrosis factor-dependent segmental control of MIG expression by high endothelial venules in inflamed lymph nodes regulates monocyte recruitment [6].
• Quantitative PCR analyses revealed the upregulation of many chemokines in the inflamed lymph node, including MCP-1 and MIG [6].

Chemical compound and disease context of Cxcl9

• 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 [8].
• IP-10, Mig, and IP-9 mRNA were detected in seven of nine allergic contact dermatitis reactions after 24-72 h, but not in sodium lauryl sulfate-induced irritant contact dermatitis reactions [9].

Biological context of Cxcl9

• Whereas Mig was not able to induce chemotaxis of eosinophils, pretreatment with Mig induced a dose-dependent inhibition of chemoattractant-induced eosinophil transmigration in vitro [10].
• CXCL9-antagonism extended graft survival significantly only in plt mice, likely due, in part, to retention of alloactivated T cells in secondary lymphoid tissue/reduction of graft-infiltrating T cells [11].
• Analysis of the kinetics of Mig expression revealed mRNA transcripts present at days 7 and 12 postinfection (p.i.) but not early (day 2) or late (day 35) in the infection [12].
• The results from Northern blot and immunostaining analyses indicate that intratumoral delivery of the murine Il-12 gene via electroporation induces accumulation of IRF7 in the nuclei of tumor cells and upregulates Mig and Stat1 expression by 15- and 5-fold, respectively, compared to intratumoral electroporation of control plasmid DNA [13].
• To better understand the role of CXCR3 interactions during CD, we characterized the effects of IP-10, MIG, I-TAC, and CXCR3+ T cells on mucosal immune responses [14].

Anatomical context of Cxcl9

• Here we report that Mig functions as a negative regulator of murine eosinophils [10].
• Monokine induced by IFN-gamma (MIG; CXC chemokine ligand (CXCL)9) is important in T lymphocyte recruitment in organ transplantation [15].
• The purpose of this investigation was to determine the effect of hyaluronan (HA) on IFN-gamma-induced Mig and IP-10 expression in mouse macrophages [16].
• In the type-1 response, CXCL9 (monokine-induced by IFNgamma) declined with age then partly recovered at 24 months parallelling lymph node IFNgamma levels [17].
• RESULTS: IP-10 and Mig were constitutively expressed by normal human colon epithelium, and their cognate receptor, CXCR3, was expressed by mucosal mononuclear cells [18].

Associations of Cxcl9 with chemical compounds

• In addition, apigenin inhibits IFNgamma-stimulated secretion of monokines, CXCL-9, and -10 in MC3T3-E1 cells [19].
• Luciferase reporter assay demonstrated that sulindac inhibited IFNgamma-induced promoter activity of the CXCL9 gene [20].
• Heparin displaces interferon-gamma-inducible chemokines (IP-10, I-TAC, and Mig) sequestered in the vasculature and inhibits the transendothelial migration and arterial recruitment of T cells [21].
• In contrast, introduction of exogenous CXCL9 into the airway at the time of allergen challenge dramatically reduced airway hyper-reactivity and eosinophil accumulation [22].
• In contrast to SEB administration, treatment with lipopolysaccharide resulted in a strong induction of IP-10 and Mig in IFN-gamma receptor-deficient mice [23].

Regulatory relationships of Cxcl9

• Interestingly, our experiments also revealed a critical role for NF-kappaB in mediating IFN-gamma-induced MIG expression independent of HA [24].
• Anti-CXCL9/Mig was administered for 2 weeks post-transplant to determine whether impairment of activated T-cell migration could further prolong cardiac allograft survival in plt recipients [11].
• This study demonstrates that MIG/CXCL9 stimulates T lymphocyte proliferation and effector cytokine production, in addition to its chemotactic effects [15].
• 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 [25].
• Collectively, these data indicate that Mig is important in contributing to host defense by promoting a protective Th1 response against viral infection of the CNS [12].

Other interactions of Cxcl9

• The increase in MIG expression by RANKL was confirmed by reverse transcription-polymerase chain reaction and Western blot analysis [26].
• 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 [27].
• 3) Interferon-gamma neutralization profoundly abrogated MIG, but had little effect on other CKs [28].
• We found that in the spleen and liver MIP-1alpha, MIP-2 and Mig were the predominant chemokines expressed [29].
• In contrast, message expression of gamma interferon, MIG, IP-10, and I-TAC peaked at 2 days [30].

Analytical, diagnostic and therapeutic context of Cxcl9

• These transcripts were partially dependent on donor IFN-gamma receptors (IFN-gammars): receptor-deficient allografts manifested up to 76% less expression, but some transcripts were highly dependent (ubiquitin D) and others relatively independent (Cxcl9) [31].
• Direct transduction of Mig cDNA into the parental tumor cell line before transplantation also results in smaller tumors [32].
• MIG (CXCL9) chemokine gene therapy combines with antibody-cytokine fusion protein to suppress growth and dissemination of murine colon carcinoma [33].
• Taken together, this combination of MIG chemokine gene therapy with tumor-targeted cytokine IL-2 provides an approach for the rational design of novel cancer immunotherapy modalities [33].
• Neutralization of the chemokine MIG/CXCL9 may have therapeutic potential for the treatment of chronic rejection after heart transplantation [34].

References