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THE COMMENSAL BACTERIA LACTOBACILLUS PLANTARUM SECRETES SOLUBLE FACTORS WHICH INHIBIT NF-kappaB AND PROTEASOME FUNCTION IN INTESTINAL EPITHELIAL CELLS
EO Petrof1, EC Claud2, Y Nakagawa1, T Abramova1, Y Guo1, T Waypa1, J Sun3, EB Chang1
1Department Medicine, University of Chicago; 2Department Pediatrics, University of Chicago, Chicago, IL; 3Department Gastroenterology & Hepatology, University of Rochester, Rochester, NY
Using both macrophage and intestinal epithelial cell lines, we show that soluble bioactive factors produced by the bacteria Lactobacillus plantarum, a common colonic commensal bacteria and probiotic, was able to inhibit NF-kappaB binding activity in multiple cell types and with different activating TLR ligands (TNFalpha, flagellin, poly dI:dC). L. plantarum conditioned media (Lp-CM) therefore was able to inhibit NF-kappaB binding activity by TNF-Receptor, MyD88-dependent and MyD88-independent pathways. Moreover, cell viability was preserved and there was no increase in cellular apoptosis at the concentrations used. Lp-CM also inhibited release of MCP-1, a chemokine found in areas of active inflammation and a downstream gene target of NF-kappaB. Lp-CM inhibited degradation of IkappaB and inhibited the chymotrypsin-like activity of the proteasome, which likely explains its inhibitory effects on NF-kappaB. Its effect on proteasome activity was direct, as demonstrated by its ability to inhibit proteasome preparations purified from mouse liver. This effect was specific, since conditioned media from other commensal bacteria such as Lactobacillus paracasei or E. coli did not elicit these same effects on NF-kappaB or the proteasome. These studies could explain some of the anti-inflammatory and beneficial effects of commensal bacteria and probiotics which have been used in the clinical setting for conditions such as inflammatory bowel disease.