title: Cytokine responses of human intestinal epithelial-like Caco-2 cells to the nonpathogenic bacterium Bacillus subtilis (natto).
abstract: Intestinal epithelial cells produce cytokines in response to pathogenic bacteria. However, cellular responses of these cells to nonpathogenic strains, such as Bacillus subtilis, are yet to be determined. In this study, we investigate whether epithelial-like human colon carcinoma Caco-2 cells produce cytokines in response to B. subtilis or B. subtilis (natto). The latter strain is utilized for manufacturing the fermented soy food "natto". Live cells of nonpathogenic B. subtilis JCM 1465(T), B. subtilis (natto) and E. coli JCM 1649(T), as well as pathogenic S. enteritidis JCM 1652 and P. aeruginosa JCM 5516 strains, induced secretion of interleukin-6 (IL-6) and/or IL-8, but not IL-7, IL-15 or tumor necrosis factor alpha (TNF-alpha). Transepithelial electrical resistance (TER) of Caco-2 cell monolayers cultured with E. coli, S. enteritidis or P. aeruginosa decreased more rapidly than that of cells cultured with B. subtilis or B. subtilis (natto). The amounts of cytokine induced by B. subtilis (natto) cells were strain-dependent. Moreover, B. subtilis (natto) cells subjected to hydrochloric acid treatment, but not autoclaving, induced a higher secretion of IL-6 and IL-8 than intact cells. Tyrosine kinase inhibitors, including AG126 and genistein, suppressed cytokine secretion. Our results suggest that the nonpathogenic B. subtilis (natto) bacterium induces cytokine responses in intestinal epithelial cells via activation of an intracellular signaling pathway, such as that of nuclear factor-kappa B (NF-kappaB).
authors.affiliation: Tokyo Metropolitan Food Technology Research Center, 1-9 Kanda Sakuma-cho, Tokyo 101-0025, Chiyoda, Japan. hosoi.tomohiro@iri.metro.tokyo.jp
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Hosoi
authors.forename: Rieko
authors.initials: R
authors.lastname: Hirose
authors.forename: Shizue
authors.initials: S
authors.lastname: Saegusa
authors.forename: Akio
authors.initials: A
authors.lastname: Ametani
authors.forename: Kan
authors.initials: K
authors.lastname: Kiuchi
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaminogawa
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018938:Caco-2 Cells / Q000378:metabolism*; D006801:Humans; D006851:Hydrochloric Acid / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D016328:NF-kappa B; D011505:Protein-Tyrosine Kinases / Q000494:pharmacology
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D016328:NF-kappa B; D011505:Protein-Tyrosine Kinases; D006851:Hydrochloric Acid