In this study, using rat carrageenin-induced pleurisy, we found that treatm
ent of rats with either indomethacin or NS398 suppressed the pleurisy at 2
h but significantly exacerbated this reaction at 48 h. Exacerbated inflamma
tion was associated with reduced prostaglandin D-2 levels, decreased heat s
hock factor 1 (HSF1) activation, reduced hsp72 expression and increased act
ivation of nuclear factor KB (NF-KB). Replacement of cyclopentenone prostag
landins 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 cyclope
ntenone prostaglandins may act as anti-inflammatory mediators by inducing i
n inflammatory cells HSF1-dependent hsp72 expression and NF-kappaB inhibiti
on, two crucial events for the remission of inflammation. (C) 2001 Federati
on of European Biochemical Societies. Published by Elsevier Science B.V. Al
l rights reserved.