{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T08:08:57Z","timestamp":1777104537195,"version":"3.51.4"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,4,25]],"date-time":"2008-04-25T00:00:00Z","timestamp":1209081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Recent studies have implicated products of cyclooxygenase 2 (COX\u20102) in not only induction but also resolution of the inflammatory response; however, the contribution of COX\u20102 products to the in vivo response to infection is unknown. The aim of this study was to determine the contribution of COX\u20102 to temporal regulation of the inflammatory response to infection in a murine model of Lyme arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Experimental Lyme disease was induced in both arthritis\u2010resistant DBA\/2J and arthritis\u2010susceptible C3H\/HeJ mice by inoculation in the hind footpads with<jats:italic>Borrelia burgdorferi<\/jats:italic>. COX\u20102 inhibitors were administered daily, and their effect on arthritis pathology was assessed at various time points postinfection. The COX\u20102 deficiency was also backcrossed onto both DBA and C3H backgrounds to confirm the findings from COX\u20102 inhibitor\u2013treated mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In COX\u20102 inhibitor\u2013treated or COX\u20102<jats:sup>\u2212\/\u2212<\/jats:sup>C3H mice, arthritis developed normally but did not resolve. Cessation of COX\u20102 inhibitor treatment on day 14 postinfection did not induce resolution of arthritis, indicating an early onset for the molecular mechanisms governing resolution. The lack of resolution of arthritis correlated with altered COX\u20102 and cytosolic phospholipase A<jats:sub>2<\/jats:sub>messenger RNA levels in the joints of C3H mice. In addition, the proresolution lipid molecule 15\u2010deoxy\u2010\u0394<jats:sup>12,14<\/jats:sup>\u2010prostaglandin J<jats:sub>2<\/jats:sub>was produced in response to<jats:italic>B burgdorferi<\/jats:italic>infection, and its production was attenuated by the inhibition of COX\u20102.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate that early production of COX\u20102 products is necessary for resolution of the inflammatory arthritis induced by<jats:italic>Borrelia<\/jats:italic>infection, and that COX\u20102 inhibition may result in prolonged inflammatory states, possibly by inhibition of proresolution eicosanoids.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.23371","type":"journal-article","created":{"date-parts":[[2008,4,25]],"date-time":"2008-04-25T21:48:42Z","timestamp":1209160122000},"page":"1485-1495","source":"Crossref","is-referenced-by-count":29,"title":["Arthritis develops but fails to resolve during inhibition of 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