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J. Biol. Chem. 277 (52): 50959-50965

© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

Probiotic Bacterium Prevents Cytokine-induced Apoptosis in Intestinal Epithelial Cells*

Fang YanDagger and D. Brent PolkDagger §

From the Departments of Dagger  Pediatrics and § Cell and Developmental Biology, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Probiotic bacteria are microorganisms that benefit the host by preventing or ameliorating disease. However, little information is known regarding the scientific rationale for using probiotics as alternative medicine. The purpose of this paper is to investigate the mechanisms of probiotic beneficial effects on intestinal cell homeostasis. We now report that one such probiotic, Lactobacillus rhamnosus GG (LGG), prevents cytokine-induced apoptosis in two different intestinal epithelial cell models. Culture of LGG with either mouse or human colon cells activates the anti-apoptotic Akt/protein kinase B. This model probiotic also inhibits activation of the pro-apoptotic p38/mitogen-activated protein kinase by tumor necrosis factor, interleukin-1alpha , or gamma -interferon. Furthermore, products recovered from LGG culture broth supernatant show concentration-dependent activation of Akt and inhibition of cytokine-induced apoptosis. These observations suggest a novel mechanism of communication between probiotic microorganisms and epithelia that increases survival of intestinal cells normally found in an environment of pro-apoptotic cytokines.

* This work was supported by a Children's Digestive Health and Nutrition Foundation/Nestle Nutrition Grant (to F. Y.), National Institutes of Health Grants DK10105 (to F. Y.) and DK56008 (to D. B. P.), and the Vanderbilt University Digestive Disease Research Center (DK58404).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Pediatric Gastroenterology, Hepatology, and Nutrition, S4322 MCN, 21st and Garland Ave., Nashville, TN 37232-2576. Tel.: 615-322-7449; Fax: 615-343-8915; E-mail:

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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