CXCL-10/CXCR3 in macrophages regulates tissue repair by controlling the expression of Arg1, VEGFa and TNFα.

ABSTRACT

Macrophages have been reported to participate in inflammation, tissue homeostasis and tissue repair. The detailed mechanism of macrophage-mediated tissue repair is not clear. CXCL-10, secreted by monocytes, endothelial cells and fibroblasts, mediates immune response and angiogenesis by binding to CXCR3. In this study, the expression of CXCL-10 and CXCR3 in porcine lung injury induced by porcine reproductive and respiratory syndrome virus (PRRSV) infection was firstly examined. The results showed that the expression of both CXCL-10 and CXCR3 increased in the infected pig lungs. In addition, the increased expression of CXCL-10 and CXCR3 in macrophage treated by poly (IC) was also observed, suggesting the autocrine system existed in macrophages. Furthermore, CXCL-10 treatment induced upregulation of Arg1 and VEGFa, and downregulation of TNFα in macrophage, and CXCR3 antagonist AMG487 treatment presented the contrary effects on the expression of Arg1, VEGFa, and TNFα. CXCL- 10-stimulated effects were dependent on PI3K/Akt signaling pathway. Wound-healing assay showed that CXCL-10 treatment macrophage conditioned medium promoted the healing process of endothelial cells. Our results suggested that CXCL-10/CXCR3 in macrophage may mediate tissue repair by regulating the macrophage expression of Arg1, VEGFa and TNFα. Modulation of CXCL-10/CXCR3 axis in macrophage may be a potential therapeutic strategy for tissue injury and repair.