Department of Basic Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei Province, P.R. China.
Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, and Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, Anhui Province, P.R. China.
J Biol Regul Homeost Agents. 2020 May-Jun;34(3):987-999. doi: 10.23812/20-59-A-65.
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 (I:C) 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.
巨噬细胞被报道参与炎症、组织稳态和组织修复。巨噬细胞介导的组织修复的详细机制尚不清楚。CXCL-10 由单核细胞、内皮细胞和成纤维细胞分泌，通过与 CXCR3 结合来介导免疫反应和血管生成。在本研究中，首先检查了猪繁殖与呼吸综合征病毒（PRRSV）感染诱导的猪肺损伤中 CXCL-10 和 CXCR3 的表达。结果表明，感染猪肺中 CXCL-10 和 CXCR3 的表达均增加。此外，还观察到 poly（I：C）处理的巨噬细胞中 CXCL-10 和 CXCR3 的表达增加，表明巨噬细胞中存在自分泌系统。此外，CXCL-10 处理诱导巨噬细胞中 Arg1 和 VEGFa 的上调和 TNFα 的下调，而 CXCR3 拮抗剂 AMG487 处理对 Arg1、VEGFa 和 TNFα 的表达呈现相反的影响。CXCL-10 刺激作用依赖于 PI3K/Akt 信号通路。伤口愈合试验表明，CXCL-10 处理的巨噬细胞条件培养基促进了内皮细胞的愈合过程。我们的结果表明，巨噬细胞中的 CXCL-10/CXCR3 可能通过调节巨噬细胞中 Arg1、VEGFa 和 TNFα 的表达来介导组织修复。调节巨噬细胞中的 CXCL-10/CXCR3 轴可能是组织损伤和修复的一种潜在治疗策略。
