Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Jiangsu, China.
Cytokine. 2013 Oct;64(1):382-94. doi: 10.1016/j.cyto.2013.05.012. Epub 2013 Jun 29.
Chemokines have been shown to play an important role in the pathogenesis of pancreatitis, but the role of chemokine CXCL9 in pancreatitis is poorly understood. The aim of this study was to investigate whether CXCL9 was a modulating factor in chronic pancreatitis. Chronic pancreatitis was induced in Sprague-Dawley rats by intraductal infusion of trinitrobenzene sulfonic acid (TNBS) and CXCL9 expression was assessed by immunohistochemistry, Western blot analysis and enzyme linked immunosorbent assay (ELISA). Recombinant human CXCL9 protein (rCXCL9), neutralizing antibody and normal saline (NS) were administered to rats with chronic pancreatitis by subcutaneous injection. The severity of fibrosis was determined by measuring hydroxyproline in pancreatic tissues and histological grading. The effect of rCXCL9 on activated pancreatic stellate cells (PSCs) in vitro was examined and collagen 1α1, TGF-β1 and CXCR3 expression was assessed by Western blot analysis in isolated rat PSCs. Chronic pancreatic injury in rats was induced after TNBS treatment and CXCL9 protein was markedly upregulated during TNBS-induced chronic pancreatitis. Although parenchymal injury in the pancreas was not obviously affected after rCXCL9 and neutralizing antibody administration, rCXCL9 could attenuate fibrogenesis in TNBS-induced chronic pancreatitis in vivo and exerted antifibrotic effects in vitro, suppressing collagen production in activated PSCs. In conclusion, CXCL9 is involved in the modulation of pancreatic fibrogenesis in TNBS-induced chronic pancreatitis in rats, and may be a therapeutic target in pancreatic fibrosis.
趋化因子在胰腺炎的发病机制中起着重要作用，但趋化因子 CXCL9 在胰腺炎中的作用知之甚少。本研究旨在探讨 CXCL9 是否是慢性胰腺炎的调节因子。通过胰管内输注三硝基苯磺酸（TNBS）诱导 Sprague-Dawley 大鼠慢性胰腺炎，通过免疫组织化学、Western blot 分析和酶联免疫吸附试验（ELISA）评估 CXCL9 的表达。通过皮下注射向慢性胰腺炎大鼠给予重组人 CXCL9 蛋白（rCXCL9）、中和抗体和生理盐水（NS）。通过测量胰腺组织中的羟脯氨酸和组织学分级来确定纤维化的严重程度。通过 Western blot 分析评估 rCXCL9 对体外激活的胰腺星状细胞（PSCs）的影响，并在分离的大鼠 PSCs 中评估胶原 1α1、TGF-β1 和 CXCR3 的表达。TNBS 处理后诱导大鼠慢性胰腺损伤，TNBS 诱导的慢性胰腺炎期间 CXCL9 蛋白明显上调。尽管 rCXCL9 和中和抗体给药后胰腺实质损伤没有明显影响，但 rCXCL9 可减轻 TNBS 诱导的慢性胰腺炎中的纤维化，并在体外发挥抗纤维化作用，抑制激活的 PSCs 中的胶原产生。总之，CXCL9 参与了 TNBS 诱导的慢性胰腺炎大鼠胰腺纤维化的调节，可能是胰腺纤维化的治疗靶点。
