Purpose. Using RAW 264.7 macrophages, the present study investigates the in
fluence of optically pure enantiomers of the nonsteroidal anti-inflammatory
drug flurbiprofen on lipopolysaccharide (LPS)induced inducible nitric oxid
e synthase (iNOS) expression.
Methods. iNOS and cyclooxygenase-2 (COX-2) mRNA levels were measured by qua
ntitative rear-time reverse-transcription polymerase chain reaction (RT-PCR
). Concentrations of nitrite (index of cellular NO production) and prostagl
andin E-2 (index of COX-2 activity) in cell culture supernatants were deter
mined by Griess assay and enzyme immunoassay, respectively.
Results. R(-)- and S(+)-flurbiprofen decreased LPS-induced iNOS mRNA and ni
trite levels in an equipotent and concentration-dependent manner. Suppressi
on of iNOS mRNA expression by R(-)and S(+)-flurbiprofen was gene-specific i
n that both substances failed to inhibit LPS-induced COX-2 mRNA expression.
By contrast, flurbiprofen enantiomers suppressed LPS-induced prostaglandin
E-2 formation enantioselectively with S(+)-flurbiprofen being considerably
more potent than its R(-)-antipode.
Conclusions. Our results show that R(-)- and S(+)-flurbiprofen, albeit diff
ering in their potency as inhibitors of COX-2 activity, equipotently suppre
ss iNOS expression. Because sustained high NO levels are associated with pa
in and tissue injury under various pathological conditions, a suppression o
f the inducible NO pathway may contribute to the pharmacological action of
both R(-)- and S(+)-flurbiprofen.