Non-prostaglandin effects of aspirin III and salicylate: inhibition of integrin-dependent human neutrophil aggregation and inflammation in COX 2- and NF kappa B (P105)-knockout mice.
Two, non-prostaglandin effects of antiinflammatory levels of salicylates (i.e. aspirin III) are shown here: 1) Exposure of neutrophils to aspirin or sodium salicylate inhibited Erk activity and integrin-dependent aggregation of neutrophils, consistent with antiinflammation but not COX inhibition. Inhibition of Mek (proximal activator of Erk) also blocked stimulation of Erk and neutrophil aggregation by FMLP and arachidonic acid. Thus, the antiinflammatory effects of salicylates may be mediated by inhibition of Erk signaling required for integrin-mediated responses. 2) Acute inflammation was induced in murine air-pouches of wild-type mice and mice rendered deficient in either COX-2 or p105, the precursor of p50 of NF kappa B. The antiinflammatory effects of aspirin and sodium salicylate were independent of the presence of COX-2 or p105 component of NF kappa B or the levels of prostaglandins at the inflammatory site. In contrast, glucocorticoid action depended on the p105.
Weissmann
Gerald
G
Division of Rheumatology, Department of Medicine, NYU School of Medicine, New York, NY 10016, USA. gerald.weissmann@med.nyu.edu
Montesinos
M Carmen
MC
Pillinger
Michael
M
Cronstein
Bruce N
BN
D000082:Acetaminophen / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002449:Cell Aggregation; D051546:Cyclooxygenase 2; D006801:Humans; D016023:Integrins / Q000172:deficiency / Q000502:physiology*; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000097:blood; D016328:NF-kappa B / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020156:Salicylic Acid / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016023:Integrins; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D000082:Acetaminophen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D020928:Mitogen-Activated Protein Kinases; D020156:Salicylic Acid; D001241:Aspirin