INDUCTION OF CYCLOOXYGENASE AND NITRIC-OXIDE SYNTHASE IN ENDOTOXIN-ACTIVATED J774 MACROPHAGES IS DIFFERENTIALLY REGULATED BY INDOMETHACIN -ENHANCED CYCLOOXYGENASE-2 PROTEIN EXPRESSION BUT REDUCTION OF INDUCIBLE NITRIC-OXIDE SYNTHASE
Lh. Pang et Jrs. Hoult, INDUCTION OF CYCLOOXYGENASE AND NITRIC-OXIDE SYNTHASE IN ENDOTOXIN-ACTIVATED J774 MACROPHAGES IS DIFFERENTIALLY REGULATED BY INDOMETHACIN -ENHANCED CYCLOOXYGENASE-2 PROTEIN EXPRESSION BUT REDUCTION OF INDUCIBLE NITRIC-OXIDE SYNTHASE, European journal of pharmacology, 317(1), 1996, pp. 151-155
The involvement of prostaglandins in feedback modulation of the lipopo
lysaccharide-inducible isoforms of cyclooxygenase and nitric oxide was
studied, This was done by testing the effects of arachidonic acid and
indomethacin in the murine macrophage cell line J774, When added befo
re lipopolysaccharide, arachidonic acid (10(-6)-10(-4) M) dose-depende
ntly reduced inducible nitric oxide synthase and cyclooxygenase-2 acti
vity as well as reducing the expression of both enzyme proteins, Indom
ethacin (10(-7)-10(-4) M) suppressed prostaglandin E(2) release into t
he medium and reduced cyclooxygenase-2 activity inversibly, as expecte
d, but the amount of cyclooxygenase 3 protein was increased (because i
ndomethacin removes the inhibitory effect of prostaglandins on cycloox
ygenase-2 expression). However, the same doses of indomethacin also in
hibited the release of nitric oxide into the medium, This was accompan
ied by a reduction in the amount of inducible nitric oxide synthase pr
otein, The drug was not cytotoxic, Thus these results show that pharma
cological treatments can have opposing actions on inducible nitric oxi
de synthase and cyclooxygenase-2 induction, with indomethacin showing
an additional unexpected action in macrophages which may diminish thei
r cytotoxic potential.