Zhuang Xiaohui, Shen Jiaqing, Jia Zhengyu, Wu Airong, Xu Ting, Shi Yuqi, Xu Chunfang
Department of Gastroenterology and Digestive Diseases, the First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
Department of Gastroenterology and Digestive Diseases, the First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
Int Immunopharmacol. 2016 Jun;35:1-6. doi: 10.1016/j.intimp.2016.03.013. Epub 2016 Mar 19.
B7-H3, a recently discovered B7 family member, is documented as a regulator in the inflammatory response as well as T cell-mediated immune responses. In this paper, we find that patients with acute pancreatitis revealed overwhelming levels of serum soluble B7-H3 (sB7-H3) associated with the clinical outcomes. Furthermore, B7-H3 protein was marked increased in l-arginine-induced acute experimental pancreatitis. Anti-B7-H3 monoclonal antibody treatment attenuated the proinflammatory cytokine production, downregulated the activation of the NF-κB signaling pathway, and ameliorated the pancreas disruption in l-arginine-induced pancreatitis. In addition, although l-arginine alone failed to induce the production of proinflammatory cytokine and anti-B7-H3 mAb had no effect on the proinflammatory cytokine production of acinar cells, administration of anti-B7-H3 mAb in the coculture model of acinar cells and macrophages stimulated by l-arginine displayed the similar effects. On the whole, B7-H3 participates in the development of acute pancreatitis, and anti-B7-H3 monoclonal antibody ameliorates severity of acute experimental pancreatitis via attenuation of the inflammatory response.
B7-H3是最近发现的一种B7家族成员，被证明是炎症反应以及T细胞介导的免疫反应中的一种调节因子。在本文中，我们发现急性胰腺炎患者血清可溶性B7-H3（sB7-H3）水平极高，且与临床结果相关。此外，在L-精氨酸诱导的急性实验性胰腺炎中，B7-H3蛋白显著增加。抗B7-H3单克隆抗体治疗可减轻促炎细胞因子的产生，下调NF-κB信号通路的激活，并改善L-精氨酸诱导的胰腺炎中的胰腺损伤。此外，虽然单独使用L-精氨酸未能诱导促炎细胞因子的产生，且抗B7-H3单克隆抗体对腺泡细胞促炎细胞因子的产生没有影响，但在L-精氨酸刺激的腺泡细胞和巨噬细胞共培养模型中给予抗B7-H3单克隆抗体显示出类似的效果。总体而言，B7-H3参与急性胰腺炎的发展，抗B7-H3单克隆抗体通过减轻炎症反应改善急性实验性胰腺炎的严重程度。
