MIG/CXCL9 Protein, Human

CXCL9 is a member of the CXC family and has an important role in the chemotaxis of immune cells. It is secreted by various cell types including immune cells (T lymphocytes, NK cells, dendritic cells, macrophages, eosinophils, etc.), and non-immune cells (hepatic stellate cells, preadipocytes, thyrocytes, endothelial cell, tumor cells, and fibroblasts, etc)^[1].
The amino acid sequence of human CXCL9 protein has low homology between mouse and rat CXCL9 protein.
CXCL9 is one of the ligands of chemokine receptor CXCR3 that mediates the infiltration of lymphocytes to focal sites and suppresses tumor growth. CXCL9 attracts CXCR3- (CXCR3-A and CXCR3-B) T lymphocytes, is involved in the pathogenesis of a variety of physiologic diseases during their initiation and their maintenance. The transcriptional regulation of CXCL9 is a multistep process involving many transcription factors, of which STAT1 and NF-κB are two most well-characterized members. Both the gene mutation of STAT1 and the blocking of the JA/STAT1 pathway can reduce CXCL9 expression induced by IFN-γ. Moreover, CXCL9 expression can be suppressed by reducing the levels of components of the STAT1-IRF-1 transcriptional activation pathway by Porphyromonas gingivalis that leads to the immune function decline. Lipopolysaccharide (LPS) and D-galactosamine could induce the phosphorylation of STAT1 and enhance the transcription of CXCL9 leading to the enhancement of liver inflammation, and even liver apoptosis and injury^[1][2][3].
CXCL9 could promote cancer metastasis via enhanced migration and invasion of tumor cells, and breaking of the endothelial cells monolayer. However, as a tumor suppressor, it mainly recruited tumor-infiltrating CD8⁺ T cells and NK cells, and inhibited tumor angiogenesis. In Addition, IL-12 and Th1-derived IFN-γ exerted antitumor effects through the inhibitory effects of endogenous CXCL9 on tumor vasculature in human Burkitt's lymphoma. In cutaneous T-cell lymphoma, expression of CXCL9 was found at early stage but low at advanced stage. CXCL9 is also associated with human hepatic fibrosis and anti-fibrosis in mice. Furthermore, CXCL9 is highly expressed in atherosclerotic plaques of coronary arteries and specifically recruits CXCR3-bearing Th1 cells that increase the risk of plaque progression and the occurrences of myocardial infarction^[1][2][3][4].

CXCL9 (10 ng/mL, 100 ng/mL; 6 h, 10 h) induces NK-92 chemotaxis, and upregulats CXCR3, PI3K (p110γ), and PLC-β3 expression, increases the level of T-bet and STAT1, which associated with NK cell activation^[6].
Thus, CXCL9 induces natural killer (NK) cells to be recruited to hepatocellular carcinoma (HCC) cells and activate NK cytotoxicity against HCC^[6].

Recombinant human CXCL9 (100 ng/mL; 5 days) up-regulates PD-L1 expression in bladder cancer T24 cells through its receptor CXCR3. And CXCL9 (72 hours) significantly enhances STAT3 and Akt activation in T24 cells^[2].
Recombinant human CXCL9 (1, 10, and 100 ng/mL; 72 or 96 h) enhanced the growth and migration of normal human cardiac fibroblasts (NHCFs)^[3].