Abstract
Rat carrageenin-induced pleurisy was used to clarify the role of prostaglandin H synthase (PGHS)-2 in acute inflammation. Intrapleural injection of 0.2 ml of 2% lambda-carrageenin induced accumulation of exudate and infiltration of leukocytes into the pleural cavity. When PGHS-1 and -2 proteins in the pleural exudate cells were analyzed by Western blot analysis, PGHS-2 was detectable from 1 hr after carrageenin injection. Its level rose sharply, remained high from 3 to 7 hr after injection, and then fell to near the detection limit. PGHS-1 was also detected, but kept almost the same level throughout the course of the pleurisy. Levels of prostaglandin (PG) E2 and thromboxane (TX) B2 in the exudate increased from hour 3 to hour 7, and then declined. Thus, the changes of the level of PGE2 were closely paralleled those of PGHS-2. The selective PGHS-2 inhibitors NS-398, nimesulide and SC-58125 suppressed the inflammatory reaction and caused a marked decrease in the level of PGE2 but not in those of TXB2 and 6-keto-PGF 1 alpha. These results suggest that the PGHS-2 expressed in the pleural exudate cells may be involved in PGE2 formation at the site of inflammation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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6-Ketoprostaglandin F1 alpha / metabolism
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Animals
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Anti-Inflammatory Agents / pharmacology
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Azo Compounds / metabolism
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Blotting, Western
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Carrageenan / pharmacology
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Cell Count / drug effects
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Cells, Cultured
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Coloring Agents / metabolism
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Cyclooxygenase Inhibitors / pharmacology
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Dexamethasone / pharmacology
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Dinoprostone / metabolism
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Excipients / pharmacology
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Inflammation / metabolism
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Isoenzymes / metabolism
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Leukocytes / drug effects
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Leukocytes / metabolism
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Male
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Nitrobenzenes / pharmacology
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Pleura / metabolism
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Prostaglandin-Endoperoxide Synthases / metabolism*
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Pyrazoles / pharmacology
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Rats
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Rats, Sprague-Dawley
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Sulfonamides / pharmacology
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Thromboxane B2 / metabolism
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Trypan Blue
Substances
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Anti-Inflammatory Agents
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Azo Compounds
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Coloring Agents
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Cyclooxygenase Inhibitors
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Excipients
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Isoenzymes
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Nitrobenzenes
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Pyrazoles
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Sulfonamides
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N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
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1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole
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pontamine sky blue
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Thromboxane B2
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6-Ketoprostaglandin F1 alpha
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Dexamethasone
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Carrageenan
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Prostaglandin-Endoperoxide Synthases
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Trypan Blue
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Dinoprostone
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nimesulide