Cyclooxygenase-independent actions of cyclooxygenase inhibitors

Citation
I. Tegeder et al., Cyclooxygenase-independent actions of cyclooxygenase inhibitors, FASEB J, 15(12), 2001, pp. 2057-2072
Citations number
218
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Experimental Biology
Journal title
FASEB JOURNAL
ISSN journal
0892-6638 → ACNP
Volume
15
Issue
12
Year of publication
2001
Pages
2057 - 2072
Database
ISI
SICI code
0892-6638(200110)15:12<2057:CAOCI>2.0.ZU;2-S
Abstract
Several studies have demonstrated unequivocally that certain nonsteroidal a nti-inflammatory drugs (NSAIDs) such as sodium salicylate, sulindac, ibupro fen, and flurbiprofen cause anti-inflammatory and antiproliferative effects independent of cyclooxygenase activity and prostaglandin synthesis inhibit ion. These effects are mediated through inhibition of certain transcription factors such as NF-kappaB and AP-1. The respective NSAIDs might interfere directly with the transcription factors, but their effects are probably med iated predominantly through alterations of the activity of cellular kinases such as IKK beta, Erk, p38 MAPK, or Cdks. These effects apparently are not shared by all NSAIDs, since indomethacin failed to inhibit NF-kappaB and A P-1 activation as well as Erk and Cdk activity. In contrast, indomethacin w as able to activate PPAR gamma, which was not affected by sodium salicylate or aspirin. The differences in cyclooxygenase-independent mechanisms may h ave consequences for the specific use of these drugs in individual patients because additional effects may either enhance the efficacy or reduce the t oxicity of the respective compounds.