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This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/G506    most recent 90553.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Watanabe, T. Articles by Arakawa, T. PubMed PubMed Citation Articles by Watanabe, T. Articles by Arakawa, T.

INFLAMMATION/IMMUNITY/MEDIATORS

Probiotic Lactobacillus casei strain Shirota prevents indomethacin-induced small intestinal injury: involvement of lactic acid

¹Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka; ²Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Kyoto; ³Yakult Central Institute for Microbiological Research, Kunitachi, Tokyo; and ⁴Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan

Submitted 18 September 2008 ; accepted in final form 14 May 2009

Inflammatory responses triggered by activation of the lipopolysaccharide (LPS)/Toll-like receptor (TLR) 4 signaling pathway are a key mechanism in nonsteroidal anti-inflammatory drug-induced enteropathy. The aim of this study was to investigate the probiotic effect of Lactobacillus casei strain Shirota (LcS) on indomethacin-induced small intestinal injury. Rats pretreated with viable LcS or heat-killed LcS once or once daily for a week were administered indomethacin by gavage to induce injury. Anti-inflammatory effects of L-lactic acid (1–15 mM) were evaluated in vitro by use of THP-1 cells. One-week treatment with viable LcS prevented indomethacin-induced intestinal injury with increase in the concentration of lactic acid in small intestinal content and inhibited increases in myeloperoxidase activity and expression of mRNA for tumor necrosis factor- (TNF-) while affecting neither TLR4 expression nor the number of gram-negative bacteria in intestinal content, whereas neither heat-killed LcS nor a single dose of viable LcS inhibited intestinal injury. Prevention of this injury was also observed in rats given L-lactic acid in drinking water. Both L-lactic acid and LcS culture supernatant containing 10 mM lactic acid inhibited NF-B activation and increases in TNF- mRNA expression and TNF- protein secretion in THP-1 cells treated with LPS. Western blot analyses showed that both L-lactic acid and LcS culture supernatants suppressed phosphorylation and degradation of I-B- induced by LPS without affecting expression of TLR4. These findings suggest that LcS exhibits a prophylactic effect on indomethacin-induced enteropathy by suppressing the LPS/TLR4 signaling pathway and that this probiotic effect of LcS may be mediated by L-lactic acid.

enteropathy; Toll-like receptor; signal transduction