{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:26:08Z","timestamp":1790029568449,"version":"4.0.1"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,5,25]]},"abstract":"<jats:p>\n                    The antiinflammatory action of aspirin generally has been attributed to direct inhibition of cyclooxygenases (COX-1 and COX-2), but additional mechanisms are likely at work. These include aspirin\u2019s inhibition of NF\u03baB translocation to the nucleus as well as the capacity of salicylates to uncouple oxidative phosphorylation (i.e., deplete ATP). At clinically relevant doses, salicylates cause cells to release micromolar concentrations of adenosine, which serves as an endogenous ligand for at least four different types of well-characterized receptors. Previously, we have shown that adenosine mediates the antiinflammatory effects of other potent and widely used antiinflammatory agents, methotrexate and sulfasalazine, both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . To determine\n                    <jats:italic>in vivo<\/jats:italic>\n                    whether clinically relevant levels of salicylate act via adenosine, via NF\u03baB, or via the \u201cinflammatory\u201d cyclooxygenase COX-2, we studied acute inflammation in the generic murine air-pouch model by using wild-type mice and mice rendered deficient in either COX-2 or p105, the precursor of p50, one of the components of the multimeric transcription factor NF\u03baB. Here, we show that the antiinflammatory effects of aspirin and sodium salicylate, but not glucocorticoids, are largely mediated by the antiinflammatory autacoid adenosine independently of inhibition of prostaglandin synthesis by COX-1 or COX-2 or of the presence of p105. Indeed, both inflammation and the antiinflammatory effects of aspirin and sodium salicylate were independent of the levels of prostaglandins at the inflammatory site. These experiments also provide\n                    <jats:italic>in vivo<\/jats:italic>\n                    confirmation that the antiinflammatory effects of glucocorticoids depend, in part, on the p105 component of NF\u03baB.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.11.6377","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"6377-6381","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":142,"title":["Salicylates and sulfasalazine, but not glucocorticoids, inhibit leukocyte accumulation by an adenosine-dependent mechanism that is independent of inhibition of prostaglandin synthesis and p105 of NF\u03baB"],"prefix":"10.1073","volume":"96","author":[{"given":"Bruce N.","family":"Cronstein","sequence":"first","affiliation":[{"name":"New York University School of Medicine, 550 First Avenue, New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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