Area Editoriale
BACKGROUND& AIMS: Increased inflammatory cytokine levels and intestinal epithelialcell apoptosis leading to disruption of epithelial integrity are majorpathologic factors in inflammatory bowel diseases. The probiotic bacteriumLactobacillus rhamnosus GG (LGG) and factors recovered from LGG broth culturesupernatant (LGG-s) prevent cytokine-induced apoptosis in human and mouseintestinal epithelial cells by regulating signaling pathways. Here, we purifyand characterize 2 secreted LGG proteins that regulate intestinal epithelialcell antiapoptotic and proliferation responses. METHODS: LGG proteins werepurified from LGG-s, analyzed, and used to generate polyclonal antibodies forimmunodepletion of respective proteins from LGG-conditioned cell culture media(CM). Mouse colon epithelial cells and cultured colon explants were treatedwith purified proteins in the absence or presence of tumor necrosis factor(TNF). Akt activation, proliferation, tissue injury, apoptosis, and caspase-3activation were determined. RESULTS: We purified 2 novel proteins, p75 (75kilodaltons) and p40 (40 kilodaltons), from LGG-s. Each of these purifiedprotein preparations activated Akt, inhibited cytokine-induced epithelial cellapoptosis, and promoted cell growth in human and mouse colon epithelial cellsand cultured mouse colon explants. TNF-induced colon epithelial damage wassignificantly reduced by p75 and p40. Immunodepletion of p75 and p40 fromLGG-CM reversed LGG-CM activation of Akt and its inhibitory effects oncytokine-induced apoptosis and loss of intestinal epithelial cells.CONCLUSIONS: p75 and p40 are the first probiotic bacterial proteinsdemonstrated to promote intestinal epithelial homeostasis through specificsignaling pathways. These findings suggest that probiotic bacterial componentsmay be useful for preventing cytokine-mediated gastrointestinal diseases. Leggil'articolo