Probiotic Escherichia coli Nissle 1917 and Commensal E. coli K12 Differentially Affect the Inflammasome in Intestinal Epithelial Cells

Background: The probiotic bacterial strain Escherichia coli Nissle 1917 (EcN) is used for the treatment of ulcerative colitis (UC), diarrhea and constipation. Its beneficial effects in the treatment of UC have been demonstrated in several controlled clinical studies; however, the mechanism of action on the cellular level is still not completely clear. The intracellular pattern recognition receptor NLRP3 is expressed in intestinal epithelial cells (IEC), activates caspase-1 within the inflammasome complex and has been implicated to play a role in the etiology of inflammatory bowel diseases. Methods: Probiotic EcN and commensal E. coli K12 were applied to IEC in vitro. Inflammasome activation, interleukin (IL)-18 release and caspase-1 activation were determined by coimmuno-precipitation, Western blot and ELISA. Apoptosis was investigated by Western blot. Results: Incubation of Caco-2 cells with EcN resulted in lower inflammasome activation and subsequent secretion of mature IL-18 as compared to the commensal strain K12. Induction of apoptosis as determined by cleavage of caspase-3 and poly (ADP-ribose) polymerase were lower in EcN-stimulated cells. Autophagy was induced by both bacterial strains, but to a higher extent by K12. Conclusion:These findings indicate that genetically very similar E. coli strains differ markedly in their ability to activate the inflammasome. (C) 2014 S. Karger AG, Basel