Submitted on June 1, 2009
Revised on August 31, 2009
Accepted on September 1, 2009
The angiogenic effect of probiotic Bacillus polyfermenticus on human intestinal microvascular endothelial cells is mediated by IL-8
Eunok Im1*, Yoon Jeong Choi, Cho Hee Kim, Claudio Fiocchi2, Charalabos Pothoulakis3, and Sang Hoon Rhee4
1 UCLA
2 Cleveland Clinic Foundation
3 David Geffen School of Medicine at UCLA
4 David Geffen School of Medicine, UCLA
* To whom correspondence should be addressed. E-mail: eim{at}mednet.ucla.edu.
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 pro-angiogenic 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, while 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 via 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.
