IL-1 beta induces synthesis of phospholipase A2-activating protein in rabbit distal colon

Abstract

In inflammatory bowel disease, the colonic mucosa is infiltrated by inflammatory cells that secrete a variety of inflammatory mediators such as interleukin-1 beta (IL-1 beta). IL-1 beta caused a delayed increase in Cl- secretion and in prostaglandin E2 (PGE2) release in rabbit distal colon. Both of these effects were abolished with cycloheximide, implying a role for protein synthesis in mediating IL-1 beta's effect. With the use of Western blot assays, the protein was identified as the phospholipase A2 (PLA2)-activating protein (PLAP). IL-1 beta caused a concentration-dependent and a time-dependent increase in PLAP levels as well as in PLA2 activity, with the maximal increase observed at an IL-1 beta concentration between 10 and 30 ng/ml reached in 2-10 min. The PLAP mRNA levels were also regulated by IL-1 beta with a similar time course. PLAP is constitutively present in the epithelial cells and in the subepithelial layer of the distal colon. These findings suggest a direct effect of IL-1 beta on intestinal epithelial cells to cause an increase in PLAP levels and phospholipase A2 activity and subsequent increase in PGE2 levels.