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Am J Physiol Gastrointest Liver Physiol 297: G999-G1008, 2009. First published September 3, 2009; doi:10.1152/ajpgi.00204.2009
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INFLAMMATION/IMMUNITY/MEDIATORS

The angiogenic effect of probiotic Bacillus polyfermenticus on human intestinal microvascular endothelial cells is mediated by IL-8

¹Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California; and ²The Cleveland Clinic Foundation, Lerner Research Institute, Cleveland, Ohio

Submitted June 1, 2009 ; accepted in final form September 1, 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-B activation, and inhibitors of NF-B 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-B/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.

inflammatory bowel diseases; wound healing; CXCR