Role of group IIA phospholipase A2 in rat colitis induced by dextran sulfate sodium.
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.
Tomita
Yasuhiko
Y
Division of Pharmacology, Discovery Research Laboratories, Shionogi and Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Jyoyama
Hirokuni
H
Kobayashi
Mika
M
Kuwabara
Kenji
K
Furue
Shingo
S
Ueno
Masahiko
M
Yamada
Katsutoshi
K
Ono
Takashi
T
Teshirogi
Isao
I
Nomura
Kouji
K
Arita
Hitoshi
H
Okayasu
Isao
I
Hori
Yozo
Y
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D003106:Colon / Q000201:enzymology* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054501:Group II Phospholipases A2; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D016264:Dextran Sulfate; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2