Ibuprofen: new explanation for an old phenomenon.
Nuclear factor-kappaB (NF-kappaB) translocation from the cytoplasm into the nucleus and the subsequent DNA binding is an essential prerequisite in the up-regulation of many pro-inflammatory genes, e.g. tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). The anti-inflammatory drug ibuprofen, thought to exert its beneficial effects mainly by suppressing the production of eicosanoids, inhibited the up-regulation of the pro-inflammatory cytokines IL-1beta and TNF-alpha. This effect was independent of the described potential of ibuprofen as a cyclooxygenase inhibitor. Ibuprofen inhibited the activation and translocation of the key transcription factor NF-kappaB by blocking the degradation of inhibitor-kappaBalpha, a protein that forms a complex with NF-kappaB, thereby preventing the release and subsequent translocation of NF-kappaB into the nucleus and the expression of inflammatory cytokines. The presented data offer a new explanation for the anti-inflammatory effect of ibuprofen.
Stuhlmeier
K M
KM
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. kstuhlme@bidmc.harvard.edu
Li
H
H
Kao
J J
JJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy*; D016328:NF-kappa B / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D007052:Ibuprofen