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- W4313406007 abstract "Abstract Lyme arthritis is a major sequela of disseminated Lyme disease that can persist despite antibiotic clearance of the etiological agent Borrelia burgdorferi. In the murine model of Lyme arthritis (mLA), infected mice develop an inflammatory arthritis characterized by robust innate cell infiltrate and synovial hyperplasia in the tibiotarsal joint, followed by spontaneous resolution around 4–5 weeks post-infection. Eicosanoids are bioactive lipid mediators that play a critical role in both the development and resolution of inflammation. As such, temporal regulation of eicosanoid class-switching from proinflammatory to proresolving is vital. In other inflammation models, late-phase cyclooxygenase (COX)-2 metabolite prostaglandin (PG) E2 skews the 5-lipoxygenase (LO) eicosanoid biosynthesis pathway away from leukotriene B4 production and towards proresolving lipoxin (LX) A4 production via 12/15-LO activity. Indeed, we have previously described a defect in mLA resolution in COX-2−/− and 5-LO−/− mice. Therefore, we hypothesize that 12/15-LO production of LXA4 is required to facilitate mLA resolution. To investigate this, we characterized mLA in 12/15-LO−/− mice and observed a pronounced resolution defect, as evidenced by significant ankle swelling and persistent innate immune infiltrate compared to wild-type mice after 4–5 weeks, despite efficient control of Borrelia burdens. We are currently investigating the mLA eicosanoid profile in 12/15LO−/− mice as well as whether exogenous treatment with LXA4 promotes mLA resolution. These experiments will determine how eicosanoids regulate inflammation resolution and may identify therapeutic targets for inflammatory diseases, including human Lyme arthritis. Supported by a grant from the NIH (R21 AR175160) and the G. Ellsworth Huggins Graduate Fellowship." @default.
- W4313406007 created "2023-01-06" @default.
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- W4313406007 date "2022-05-01" @default.
- W4313406007 modified "2023-09-25" @default.
- W4313406007 title "12/15-lipoxygenase is required for inflammation resolution in a murine model of Lyme arthritis" @default.
- W4313406007 doi "https://doi.org/10.4049/jimmunol.208.supp.111.20" @default.
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