Disease relevance of Cxcr3

• 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 [1].
• After all, we did not neutralize the activity of other chemokines that bind CXCR3 (i.e., macrophage-induced gene and IFN-inducible T cell alpha chemoattractant) and yet significantly blocked not only adjuvant-induced arthritis but also the in vivo competence to mount delayed-type hypersensitivity [2].

High impact information on Cxcr3

• Expressions of neither of IP-10 nor of CXCR3 were detected on the inflammatory cells [3].
• Intragraft mRNA levels for chemokines (regulated on activation normal T cell expressed and secreted, macrophage inflammatory protein-1alpha, chemokine receptors (CCR1, CXCR3, CXCR5), IL-2, and intercellular adhesion molecule-1 were significantly decreased in CO-treated than in air-treated allografts [4].
• Discovery of structurally diverse natural product antagonists of chemokine receptor CXCR3 [1].
• 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 [1].
• Induction of the third CXCR3 ligand, CXCL11/I-TAC was not seen in the draining LN, whereas all three CXCR3 ligands and CXCR3 itself were markedly detected in the spinal cords following the development of EAE [5].

Biological context of Cxcr3

• Induction of gene expression of CXCL9/Mig and CXCL10 and their receptor CXCR3 was confirmed in the draining LN in EAE rats [5].
• In vivo administration of decoy chemokine receptor plasmid DNAs encoding the binding sites of CXCR3 and CCR2 suppressed the development of relapse of CR-EAE [6].

Anatomical context of Cxcr3

• Interestingly, immunohistochemical staining for CXCR3 showed a unique pattern of expression: we found weak expression on cells in the outer layer of the neointima and adventitia and found the strongest staining in the innermost layer of the neointima [7].
• CXCR3 and CCR4 thus appear to be available as markers for Th1/Th2 subsets in the synovia of AA rats [8].

Associations of Cxcr3 with chemical compounds

• IL10 inhibited TNFalpha, MIP-1alpha, and RANTES release of LPS-stimulated MG cells as well as TNFalpha, MIP-1alpha, and CXCR3 mRNA expression by HAPI cells after exposure to LPS (P < 0.05) [9].

Regulatory relationships of Cxcr3

• 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 [5].

Other interactions of Cxcr3

• As to their receptors, the levels of CCR1, CCR2, and CXCR3 mRNAs showed significant and prominent elevations, CCR5 mRNA also increased moderately, and their receptor protein-expressing cells also increased [10].
• In HAPI cell cultures similar stimulation of mRNA levels was found for TNFalpha, MIP-1alpha, CXCR3, and CX3CR1 [9].

Analytical, diagnostic and therapeutic context of Cxcr3

• CXCR3 chemokines are of particular interest because of their potential involvement in a variety of inflammatory diseases, including the rejection of organ transplants [11].

References