論文 - 詳細
RRC ID | 19344 |
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著者 | Watanabe T, Nishio H, Tanigawa T, Yamagami H, Okazaki H, Watanabe K, Tominaga K, Fujiwara Y, Oshitani N, Asahara T, Nomoto K, Higuchi K, Takeuchi K, Arakawa T. |
タイトル | Probiotic Lactobacillus casei strain Shirota prevents indomethacin-induced small intestinal injury: involvement of lactic acid. |
ジャーナル | Am J Physiol Gastrointest Liver Physiol |
Abstract |
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-alpha (TNF-alpha) 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-kappaB activation and increases in TNF-alpha mRNA expression and TNF-alpha 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-kappaB-alpha 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. |
巻・号 | 297(3) |
ページ | G506-13 |
公開日 | 2009-9-1 |
DOI | 10.1152/ajpgi.90553.2008 |
PII | 90553.2008 |
PMID | 19589943 |
MeSH | Animals Cell Line Disease Models, Animal Humans I-kappa B Proteins / metabolism Indomethacin Intestinal Diseases / chemically induced Intestinal Diseases / metabolism Intestinal Diseases / microbiology Intestinal Diseases / prevention & control* Intestine, Small / metabolism Intestine, Small / microbiology* Intestine, Small / pathology Lactic Acid / administration & dosage Lactic Acid / metabolism* Lactobacillus casei / isolation & purification Lactobacillus casei / metabolism* Male Monocytes / metabolism NF-KappaB Inhibitor alpha NF-kappa B / metabolism Peroxidase / metabolism Phosphorylation Probiotics* RNA, Messenger / metabolism Rats Rats, Wistar Toll-Like Receptor 4 / metabolism Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism |
IF | 3.725 |
引用数 | 93 |
WOS 分野 | PHYSIOLOGY GASTROENTEROLOGY & HEPATOLOGY |
リソース情報 | |
ヒト・動物細胞 | THP-1(RCB1189) |