Although group IIA
phospholipase A(2) has been suggested to be implicated in
inflammatory bowel disease, its pathophysiological role in
colitis remains unclear. We investigated whether group IIA
phospholipase A(2) had pro-inflammatory roles in
dextran sulfate sodium-induced
colitis in the rat. Secretory
phospholipase A(2) activity was markedly increased in the distal colon with two peaks. Strong immunostaining for group IIA
phospholipase A(2) was found in subepithelial tissue and lamina propria at early stage and in deeper tissues of the erosion area at later stage. Treatment with a specific group IIA
phospholipase A(2) inhibitor, S-3013/
LY333013 (methyl[[3-(aminooxoacetyl)-2-ethyl-1-(phenylmethyl)]-1H-indol-4yl]oxy)
acetate), reduced erosion area, shortening of colon and colonic
inflammation, and strongly inhibited the increase in secretory
phospholipase A(2) activity and moderately reduced
myeloperoxidase activity in the colon in vivo, while
eicosanoid levels were not affected. Marked group IIA
phospholipase A(2) expression in the erosion area and the improvement of
colitis by the group IIA
phospholipase A(2) inhibitor strongly suggest that this
enzyme plays pro-inflammatory roles in this
colitis model.