|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1996 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1995 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1994 : ¥700,000 (Direct Cost : ¥700,000)
Using rat carrageenin-induced pleurisy as an acute inflammatory model, the following results were obtained. 1) COX-2 mRNA and protein were detectable in cells in the pleural exudate. Change of COX-2 protein level was closely paralleled those of plasma exudation rate and PGE2 levels in the exudate. COX-1 was also detectable, but kept almost the same level throughout the course of the pleurisy. 2) The selective COX-2 inhibitors NS-398, nimesulide and SC-58125 suppressed the inflammatory reaction an caused a marked decrease in the level of PGE2 but not in those of TXB2 and 6-keto-PGF1alpha. These results suggest that the COX-2 expressed in the pleural exudate cells may be involved in PGE2 formation at the site of inflammation. 3) Dexamethasone (0.3-30 mg/kg, i.p.) markedly suppressed leukocyte infiltration and plasma exudation. Although the agent also suppressed COX-2 expression at higher doses (>3 mg/kg), it never affected at a lower dose (0.3 mg/kg). These results suggest the involvement of other mechanism (s) than inhibition of COX-2 expression as mechanisms of anti-inflammatory steroids. 4) At 5 hr after carrageenin injection, 92.0% of the cells were PMN leukocytes with a small number of mononuclear leukocytes. Both PMN and mononuclear leukocytes expressed PGHS-2, but there exist difference in pattern of COX-2 expresion. The most mononuclear cells expressed COX-2 intensively, but small number of PMN leukocytes expressed it intensively. Thus both types of cells may equally contribute to the total amount of COX-2 in the inflammatory site. 5) Among TNFalpha, IL-1alpha, IL-1beta, IL-6, CINC-1 and MCP-1, only TNFalpha (10 pmole) induced COX-2 expression by intrapleural injection.