The angiogenic effect of probiotic Bacillus polyfermenticus on human intestinal microvascular endothelial cells is mediated by IL-8.
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.
Im
Eunok
E
Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA. eim@mednet.ucla.edu
Choi
Yoon Jeong
YJ
Kim
Cho Hee
CH
Fiocchi
Claudio
C
Pothoulakis
Charalabos
C
Rhee
Sang Hoon
SH
D000818:Animals; D001407:Bacillus / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D017077:Culture Media, Conditioned / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism* / Q000494:pharmacology; D007422:Intestines / Q000098:blood supply* / Q000382:microbiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010671:Phenylurea Compounds / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D019936:Probiotics / Q000378:metabolism* / Q000627:therapeutic use; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D022502:Stress Fibers / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D017077:Culture Media, Conditioned; D016209:Interleukin-8; D016328:NF-kappa B; D010671:Phenylurea Compounds; D023063:Receptors, Interleukin-8B; C112019:SB 225002; D042461:Vascular Endothelial Growth Factor A