1 The nonsteroidal drug ibuprofen exists as an R(7)-and S(+)-enantiomer. Only the S(+)-enantiomer is an e ective cyclo-oxygenase inhibitor, while the R(7)-enantiomer is inactive in this respect. Thus the molecular mechanism by which R(7)-ibuprofen exerts its anti-in¯ammatory and antinociceptive e ects remains unknown. 2 In this study the e ects of the enantiomers of ibuprofen on modulation of transcription factors have been examined with electrophoretic mobility-shift assay (EMSA), transient transfection experiments, confocal immuno¯uorescence and nuclear import experiments, to determine their selectivity and potency as inhibitors of the activation of transcription factor nuclear factor-kB (NF-kB). 3 R(7)-ibuprofen (IC 50 : 121.8 mM) as well as the S(+)-enantiomer (IC 50 : 61.7 mM) inhibited the activation of NF-kB in response to T-cell stimulation. The e ect of ibuprofen was speci®c because, at concentrations up to 10 mM, ibuprofen did not a ect the heat shock transcription factor (HSF) and the activation of NF-kB by prostaglandin E 2 (PGE 2 ). Very high concentrations of ibuprofen (20 mM) did not prevent NF-kB binding to DNA in vitro. Immuno¯uorescence and nuclear import experiments indicate that the site of ibuprofen action appeared to be upstream of the dissociation of the NF-kB-IkBcomplex. 4 Our data raise the possibility that R(7)-ibuprofen exerts some of its e ects by inhibition of NF-kB activation.
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