Flurbiprofen enantiomers inhibit inducible nitric oxide synthase expression in RAW 264.7 macrophages.

TY - JOUR

T1 - Flurbiprofen enantiomers inhibit inducible nitric oxide synthase expression in RAW 264.7 macrophages.

AU - Hinz, B

AU - Brune, K

AU - Rau, Thomas

AU - Pahl, A

PY - 2001

Y1 - 2001

N2 - PURPOSE: Using RAW 264.7 macrophages, the present study investigates the influence of optically pure enantiomers of the nonsteroidal anti-inflammatory drug flurbiprofen on lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expression. METHODS: iNOS and cyclooxygenase-2 (COX-2) mRNA levels were measured by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR). Concentrations of nitrite (index of cellular NO production) and prostaglandin E2 (index of COX-2 activity) in cell culture supernatants were determined by Griess assay and enzyme immunoassay, respectively. RESULTS: R(-)- and S(+)-flurbiprofen decreased LPS-induced iNOS mRNA and nitrite levels in an equipotent and concentration-dependent manner. Suppression of iNOS mRNA expression by R(-)- and S(+)-flurbiprofen was gene-specific in that both substances failed to inhibit LPS-induced COX-2 mRNA expression. By contrast, flurbiprofen enantiomers suppressed LPS-induced prostaglandin E2 formation enantioselectively with S(+)-flurbiprofen being considerably more potent than its R(-)-antipode. CONCLUSIONS: Our results show that R(-)- and S(+)-flurbiprofen, albeit differing in their potency as inhibitors of COX-2 activity, equipotently suppress iNOS expression. Because sustained high NO levels are associated with pain and tissue injury under various pathological conditions, a suppression of the inducible NO pathway may contribute to the pharmacological action of both R(-)- and S(+)-flurbiprofen.

AB - PURPOSE: Using RAW 264.7 macrophages, the present study investigates the influence of optically pure enantiomers of the nonsteroidal anti-inflammatory drug flurbiprofen on lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expression. METHODS: iNOS and cyclooxygenase-2 (COX-2) mRNA levels were measured by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR). Concentrations of nitrite (index of cellular NO production) and prostaglandin E2 (index of COX-2 activity) in cell culture supernatants were determined by Griess assay and enzyme immunoassay, respectively. RESULTS: R(-)- and S(+)-flurbiprofen decreased LPS-induced iNOS mRNA and nitrite levels in an equipotent and concentration-dependent manner. Suppression of iNOS mRNA expression by R(-)- and S(+)-flurbiprofen was gene-specific in that both substances failed to inhibit LPS-induced COX-2 mRNA expression. By contrast, flurbiprofen enantiomers suppressed LPS-induced prostaglandin E2 formation enantioselectively with S(+)-flurbiprofen being considerably more potent than its R(-)-antipode. CONCLUSIONS: Our results show that R(-)- and S(+)-flurbiprofen, albeit differing in their potency as inhibitors of COX-2 activity, equipotently suppress iNOS expression. Because sustained high NO levels are associated with pain and tissue injury under various pathological conditions, a suppression of the inducible NO pathway may contribute to the pharmacological action of both R(-)- and S(+)-flurbiprofen.

M3 - SCORING: Zeitschriftenaufsatz

VL - 18

SP - 151

EP - 156

JO - PHARM RES-DORDR

JF - PHARM RES-DORDR

SN - 0724-8741

IS - 2

M1 - 2

ER -