Inactivation of Group 1B Phospholipase A(2) Enhances Disease Recovery and Reduces Experimental Colitis in Mice

Phospholipase A(2) (PLA(2)) enzymes influence inflammatory bowel disease in both positive and negative manners depending on the type of PLA(2) that is expressed. This study explored the influence of the abundantly expressed Group 1B PLA(2) (PLA2G1B) on ulcerative colitis. Wild-type C57BL/6J mice and Pla2g1b(−/−) mice were treated with dextran sulfate sodium (DSS) for 5 days to induce epithelial injury, followed by another 5 days without DSS for recovery. The Pla2g1b(−/−) mice displayed significantly less body weight loss, colitis pathology, and disease activity indexes compared to the wild-type mice. The differences in colitis were not due to differences in the colonic lysophospholipid levels, but higher numbers of stem and progenitor cells were found in the intestines of Pla2g1b(−/−) mice compared to the wild-type mice. The DSS-treated Pla2g1b(−/−) mice also showed higher expressions of genes that are responsible for epithelial repair and lower expressions of proinflammatory cytokine genes in the colon, as well as reduced inflammatory cytokine levels in the plasma. In vitro experiments revealed the PLA2G1B stimulation of inflammatory cytokine expression by myeloid cells. PLA2G1B inactivation protects against DSS-induced colitis in mice by increasing the intestinal stem cell reservoir for epithelial repair and reducing myeloid cell inflammation in the diseased colon. Thus, PLA2G1B may be a target for colitis management.