Sci. Signal., 31 May 2011
Gut Biology Bacteria Promote Repair
Nancy R. Gough
Science Signaling, AAAS, Washington, DC 20005, USA
Wounds in the epithelial layer of the gastrointestinal tract are repaired through a process called epithelial restitution that involves migration of the surrounding epithelial cells into the injured area, whereas mucosal ulceration requires cell proliferation. Following on previous studies noting that commensal bacteria induce the production of reactive oxygen species (ROS) in intestinal epithelial cells and that ROS inactivate protein tyrosine phosphatases (PTPs) and stimulate cell migration, Swanson et al. evaluated the role of the bacterially induced ROS in epithelial restitution. Exposure of cultured intestinal epithelial cell lines or whole-mount preparations of murine intestine to Lactobacillus rhamnosus strain GG (LGG) stimulated the production of ROS. Cultured intestinal epithelial cell lines exposed to LGG also exhibited decreased activity of the PTPs LMW-PTP and SHP-2 and increased phosphorylation of focal adhesion kinase (FAK), an enzyme involved in the dynamic regulation of cell attachment sites called focal adhesions. These effects were eliminated by exposure of the cells to ROS scavengers or an inhibitor of NADPH oxidases. FAK phosphorylation occurred in cells exposed to nonviable bacteria, suggesting that bacterial invasion was not required for the activation of these pathways. Stimulation of FAK phosphorylation was also observed in ex vivo preparations of mouse colon exposed to commensal bacteria or of mice injected with LGG into surgically closed ileal loops. In vitro, LGG stimulated migration of an intestinal epithelial cell line, which was blocked by inhibition of ROS production or FAK activity. In mice with injured epithelium in the small intestine due to exposure to dextran sodium sulfate, oral gavage with LGG resulted in improved epithelial barrier function and reduced inflammation, and these effects were abolished by inhibition of FAK activity. Thus, the presence of commensal bacteria in the gut provides a beneficial signal to the epithelial cells that promotes barrier repair.
P. A. Swanson II, A. Kumar, S. Samarin, M. Vijay-Kumar, K. Kundu, N. Murthy, J. Hansen, A. Nusrat, A. S. Neish, Enteric commensal bacteria potentiate epithelial restitution via reactive oxygen species-mediated inactivation of focal adhesion kinase phosphatases. Proc. Natl. Acad. Sci. U.S.A. 108, 8803–8808 (2011). [Abstract] [Full Text]
Citation: N. R. Gough, Bacteria Promote Repair. Sci. Signal. 4, ec155 (2011).
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