{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T17:48:23Z","timestamp":1792259303874,"version":"4.4.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T00:00:00Z","timestamp":1681776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Infection of C3H\/HeJ (C3H) mice with <jats:italic>Borrelia burgdorferi<\/jats:italic> results in the development of a robust inflammatory arthritis that peaks around 3-4 weeks post-infection and then spontaneously resolves over the next few weeks. Mice lacking cyclooxygenase (COX)-2 or 5-lipoxygenase (5-LO) activity develop arthritis similar to wild-type mice but display delayed or prolonged joint resolution. Since 12\/15-lipoxygenase (12\/15-LO) activity is generally down-stream of both COX-2 and 5-LO activity and results in the production of pro-resolution lipids such as lipoxins and resolvins among others, we investigated the impact of 12\/15-LO deficiency on the resolution of Lyme arthritis in mice on a C3H background. We found the expression of <jats:italic>Alox15<\/jats:italic> (12\/15-LO gene) peaked around 4-weeks post-infection in C3H mice suggesting a role for 12\/15-LO in mediating arthritis resolution. A deficiency in 12\/15-LO resulted in exacerbated ankle swelling and arthritis severity during the resolution phase without compromising anti-<jats:italic>Borrelia<\/jats:italic> antibody production and spirochete clearance. However, clearance of inflammatory cells was impeded. Therapeutic treatment of <jats:italic>B. burgdorferi<\/jats:italic>-infected C3H mice with lipoxin A4 (LXA<jats:sub>4<\/jats:sub>) near the peak of disease resulted in significantly decreased ankle swelling and a switch of joint macrophages to a resolving phenotype but did not directly impact arthritis severity. These results demonstrate that 12\/15-LO lipid metabolites are important components of inflammatory arthritis resolution in murine Lyme arthritis and may be a therapeutic target for treatment of joint edema and pain for Lyme arthritis patients without compromising spirochete clearance.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1144172","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T04:21:09Z","timestamp":1681791669000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["12\/15-lipoxygenase activity promotes efficient inflammation resolution in a murine model of Lyme arthritis"],"prefix":"10.3389","volume":"14","author":[{"given":"Christa D.","family":"Jackson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinsey 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