Role of cyclopentenone prostaglandins in rat carrageenin pleurisy.
In this study, using rat carrageenin-induced pleurisy, we found that treatment of rats with either indomethacin or NS-398 suppressed the pleurisy at 2 h but significantly exacerbated this reaction at 48 h. Exacerbated inflammation was associated with reduced prostaglandin D(2) levels, decreased heat shock factor 1 (HSF1) activation, reduced hsp72 expression and increased activation of nuclear factor kappaB (NF-kappaB). Replacement of cyclopentenone prostaglandins by treating rats with either prostaglandin J(2) or prostaglandin D(2) reversed the exacerbating effects of cyclooxygenase inhibitors leading to the resolution of the reaction. In conclusion, we demonstrate that cyclopentenone prostaglandins may act as anti-inflammatory mediators by inducing in inflammatory cells HSF1-dependent hsp72 expression and NF-kappaB inhibition, two crucial events for the remission of inflammation.
Ianaro
A
A
Department of Experimental Pharmacology, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy. ianaro@unina.it
Ialenti
A
A
Maffia
P
P
Pisano
B
B
Di Rosa
M
M
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002351:Carrageenan; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004338:Drug Combinations; D005122:Exudates and Transudates / Q000737:chemistry / Q000166:cytology; D050884:HSP72 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D009578:Nitrobenzenes / Q000494:pharmacology; D010994:Pleura / Q000187:drug effects / Q000378:metabolism*; D010998:Pleurisy / Q000139:chemically induced / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D011453:Prostaglandins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D051996:Transcription Factor RelA; D014157:Transcription Factors
D016861:Cyclooxygenase Inhibitors; D004268:DNA-Binding Proteins; D004338:Drug Combinations; C000619706:HSF1 protein, human; D050884:HSP72 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C000619709:Hsf1 protein, rat; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009578:Nitrobenzenes; D011453:Prostaglandins; D013449:Sulfonamides; D051996:Transcription Factor RelA; D014157:Transcription Factors; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C037112:9-deoxy-delta-9-prostaglandin D2; D002351:Carrageenan; D015230:Prostaglandin D2; D007213:Indomethacin