title: Nonpathogenic Escherichia coli strain Nissle 1917 inhibits signal transduction in intestinal epithelial cells.
abstract: Although the probiotic Escherichia coli strain Nissle 1917 has been used for the treatment of inflammatory bowel diseases, the precise mechanisms of action of this strain remain unclear. In the present study, we estimated the anti-inflammatory effect of E. coli Nissle 1917 on inflammatory responses in vitro to determine the suppressive mechanism of Nissle 1917 on the inflammatory process. To determine the effect of E. coli Nissle 1917, the human colonic epithelial cell line HCT15 was incubated with or without E. coli Nissle 1917 or another nonpathogenic E. coli strain, K-12, and then tumor necrosis factor alpha (TNF-alpha)-induced interleukin-8 (IL-8) production from HCT15 cells was assessed. Enzyme-linked immunosorbent assays and real-time quantitative PCR showed that Nissle 1917 treatment suppressed TNF-alpha-induced IL-8 transcription and production. In addition, results from luciferase assays indicated that Nissle 1917 inhibited IL-8 promoter activity. On the other hand, these anti-inflammatory effects were not seen with E. coli K-12. In addition, heat-killed Nissle 1917 or its genomic DNA did not have this anti-inflammatory effect. Surprisingly, Nissle 1917 did not affect IL-8 transactivation pathways, such as NF-kappaB activation, nuclear translocation, and DNA binding, or even activation of other transcriptional factors. Furthermore, it also became evident that Nissle 1917 induced the anti-inflammatory effect without contact to epithelial cells. In conclusion, these data indicate that the nonpathogenic E. coli strain Nissle 1917 expresses a direct anti-inflammatory activity on human epithelial cells via a secreted factor which suppresses TNF-alpha-induced IL-8 transactivation through mechanisms different from NF-kappaB inhibition.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kamada
authors.forename: Kenichi
authors.initials: K
authors.lastname: Maeda
authors.forename: Nagamu
authors.initials: N
authors.lastname: Inoue
authors.forename: Tadakazu
authors.initials: T
authors.lastname: Hisamatsu
authors.forename: Susumu
authors.initials: S
authors.lastname: Okamoto
authors.forename: Kyong Su
authors.initials: KS
authors.lastname: Hong
authors.forename: Takaya
authors.initials: T
authors.lastname: Yamada
authors.forename: Noriaki
authors.initials: N
authors.lastname: Watanabe
authors.forename: Kanji
authors.initials: K
authors.lastname: Tsuchimoto
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Ogata
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology*; D004926:Escherichia coli / Q000145:classification* / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha