Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA.
Am J Physiol Gastrointest Liver Physiol. 2009 Nov;297(5):G999-G1008. doi: 10.1152/ajpgi.00204.2009.
Angiogenesis is required for wound healing and repair, but dysregulated angiogenesis is involved in gastrointestinal inflammation. Bacillus polyfermenticus (B.P.) is a probiotic bacterium clinically used for a variety of intestinal disorders in East Asia. Here we investigated the effect of B.P. on angiogenesis of human intestinal microvascular endothelial cells (HIMECs) and wound healing in intestinal mucosa. Exposure of HIMECs to the conditioned medium of B.P. cultures (B.P. CM) increased cell migration, permeability, and tube formation. Production of the proangiogenic cytokine IL-8 was increased by B.P. CM, and neutralizing antibodies against IL-8 or IL-8 receptor CXCR2 reduced tube formation as well as actin stress fiber formation. B.P. CM also increased NF-kappaB activation, and inhibitors of NF-kappaB suppressed B.P. CM-induced tube formation and IL-8 production. Furthermore, B.P. facilitated recovery of mice from colitis as shown by increased body weight and reduced rectal bleeding and histological severity. B.P. also increased angiogenesis and mouse IL-8 production in the mucosal layer. Collectively, these results show that B.P. increases angiogenesis of HIMECs in a NF-kappaB/IL-8/CXCR2-dependent manner. Moreover, B.P. promotes angiogenesis in the mucosa during recovery of mice from colitis, suggesting that this probiotic may be clinically used to facilitate intestinal wound healing.
血管生成对于伤口愈合和修复是必需的，但失调的血管生成与胃肠道炎症有关。多粘类芽孢杆菌（B.P.）是一种临床用于东亚多种肠道疾病的益生菌。在这里，我们研究了 B.P. 对人肠道微血管内皮细胞（HIMEC）血管生成和肠道黏膜愈合的影响。B.P. 培养物的条件培养基（B.P. CM）暴露于 HIMEC 可增加细胞迁移、通透性和管状形成。B.P. CM 增加了促血管生成细胞因子 IL-8 的产生，中和抗 IL-8 或 IL-8 受体 CXCR2 的抗体也减少了管状形成以及肌动蛋白应激纤维的形成。B.P. CM 还增加了 NF-kappaB 的激活，NF-kappaB 的抑制剂抑制了 B.P. CM 诱导的管状形成和 IL-8 的产生。此外，B.P. 促进了结肠炎小鼠的恢复，表现为体重增加、直肠出血减少和组织学严重程度降低。B.P. 还增加了黏膜层中的血管生成和小鼠 IL-8 的产生。总的来说，这些结果表明，B.P. 通过 NF-kappaB/IL-8/CXCR2 依赖性途径增加 HIMEC 的血管生成。此外，B.P. 在结肠炎小鼠恢复期间促进了黏膜中的血管生成，这表明这种益生菌可能在临床上用于促进肠道伤口愈合。
