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J Med Microbiol. 2009 May;58(Pt 5):535-45. doi: 10.1099/jmm.0.005801-0.

Commensal bacteria can enter colonic epithelial cells and induce proinflammatory cytokine secretion: a possible pathogenic mechanism of ulcerative colitis.

Author information

1
Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, Kashiwa, Chiba 277-8567, Japan. ohkusa@jikei.ac.jp

Abstract

Interleukin 2 (IL-2)- and IL-10-knockout mice develop spontaneous colitis under conventional but not germ-free conditions, suggesting that commensal bacteria play an important role in the pathogenesis of colitis. However, interactions between commensal bacteria and colonic epithelial cells have not been fully investigated. We therefore assessed the ability of various commensal bacteria and probiotics to adhere to and invade colonic epithelial cells. Effects of the bacteria on production of proinflammatory cytokines were also measured. Commensal bacteria, including mucosal organisms isolated from ulcerative colitis (UC) patients, such as Fusobacterium varium, reported as a possible pathogen in UC, Bacteroides vulgatus, Escherichia coli and Clostridium clostridioforme, as well as their type strains and probiotics, were assessed for their ability to adhere to and invade colonic epithelial cells using two cell lines, SW-480 and HT-29. Our experiments employed co-incubation, a combination of scanning and transmission electron microscopy and recovery of bacteria from infected-cell lysates. F. varium and several other commensal bacteria, but not probiotics, adhered to colonic epithelial cells and invaded their cytoplasm. ELISA and real-time PCR revealed that the host cells, particularly those invaded by F. varium, showed significant increases in IL-8 and TNF-alpha concentrations in supernatants, with elevation of IL-8, TNF-alpha, MCP-1 and IL-6 mRNAs. Furthermore, IL-8 and TNF-alpha expression and nuclear phosphorylated NF-kappaB p65 expression could be immunohistochemically confirmed in inflamed epithelium with cryptitis or crypt abscess in UC patients. Certain commensal bacteria can invade colonic epithelial cells, activating early intracellular signalling systems to trigger host inflammatory reactions.

PMID:
19369513
PMCID:
PMC2887547
DOI:
10.1099/jmm.0.005801-0
[Indexed for MEDLINE]
Free PMC Article

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