Are the anti-inflammatory effects of dexamethasone responsible for inhibition of the induction of enzymes involved in prostanoid formation in rat carrageenin-induced pleurisy?
Since anti-inflammatory steroids modulate multiple gene expression, including the expression of prostaglandin H synthase-2 and phospholipase A(2), at the molecular level, we studied the effects of dexamethasone on rat carrageenin-induced pleurisy to elucidate whether regulation of phospholipase A(2) and prostaglandin H synthase-2 expression is the primary mechanism of its anti-inflammatory action. Suppression of plasma exudation by a lower dose of dexamethasone (0.3 mg/kg) was almost equal to that by aspirin (100 mg/kg), but that by higher dexamethasone doses (3 and 30 mg/kg) was considerably stronger, suggesting the involvement of effects other than that on prostanoid formation. The lower dose of dexamethasone also significantly reduced the pleural exudate neutrophil count and prostanoid levels. However, this dose affected neither the prostaglandin H synthase-2 level nor the phospholipase A(2) activity in the exudate cells. The prostaglandin H synthase-2 level was affected only at the higher doses, while phospholipase A(2) activity was not. These results suggest that the anti-inflammatory effects of dexamethasone in acute inflammation cannot be ascribed to direct interference with prostanoid formation via suppression of phospholipase A(2) and prostaglandin H synthase-2 expression.
Department of Pharmacology, Kitasato University School of Medicine, Kitasato 1-15-1, Kanagawa 228-8555, Sagamihara, Japan.
M
M
Kawamura
K
K
Hatanaka
M
M
Saito
M
M
Ogino
T
T
Ono
K
K
Ogino
S
S
Matsuo
Y
Y
Harada
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010741:Phospholipases A / Q000378:metabolism; D010998:Pleurisy / Q000188:drug therapy* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D007527:Isoenzymes; D011453:Prostaglandins; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A