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Infection and Immunity, January 2008, p. 214-220, Vol. 76, No. 1
0019-9567/08/$08.00+0     doi:10.1128/IAI.01193-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Nonpathogenic Escherichia coli Strain Nissle 1917 Inhibits Signal Transduction in Intestinal Epithelial Cells

Nobuhiko Kamada,^1, Kenichi Maeda,^2, Nagamu Inoue,¹ Tadakazu Hisamatsu,¹ Susumu Okamoto,¹ Kyong Su Hong,² Takaya Yamada,³ Noriaki Watanabe,⁴ Kanji Tsuchimoto,⁴ Haruhiko Ogata,¹ and Toshifumi Hibi^1*

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan,¹ Research Center, Research Division, JCR Pharmaceuticals Co., Ltd., Kobe, Japan,² Department of Experimental Animals, Center for Integrated Research in Science, Shimane University, Izumo, Japan,³ Department of Internal Medicine, Kitasato Institute Hospital, Tokyo, Japan⁴

Received 30 August 2007/ Returned for modification 28 September 2007/ Accepted 18 October 2007

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-)-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--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-B 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--induced IL-8 transactivation through mechanisms different from NF-B inhibition.

Published ahead of print on 29 October 2007.

Editor: R. P. Morrison

N.K. and K.M. contributed equally to this work.