{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:03:46Z","timestamp":1790737426701,"version":"4.1.0"},"reference-count":116,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T00:00:00Z","timestamp":1686700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Lipoxin A4 (LXA\n                      <jats:sub>4<\/jats:sub>\n                      ) has anti-inflammatory and pro-resolutive roles in inflammation. We evaluated the effects and mechanisms of action of LXA4 in titanium dioxide (TiO\n                      <jats:sub>2<\/jats:sub>\n                      ) arthritis, a model of prosthesis-induced joint inflammation and pain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Mice were stimulated with TiO\n                      <jats:sub>2<\/jats:sub>\n                      (3mg) in the knee joint followed by LXA\n                      <jats:sub>4<\/jats:sub>\n                      (0.1, 1, or 10ng\/animal) or vehicle (ethanol 3.2% in saline) administration. Pain-like behavior, inflammation, and dosages were performed to assess the effects of LXA\n                      <jats:sub>4<\/jats:sub>\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      LXA\n                      <jats:sub>4<\/jats:sub>\n                      reduced mechanical and thermal hyperalgesia, histopathological damage, edema, and recruitment of leukocytes without liver, kidney, or stomach toxicity. LXA\n                      <jats:sub>4<\/jats:sub>\n                      reduced leukocyte migration and modulated cytokine production. These effects were explained by reduced nuclear factor kappa B (NF\u03baB) activation in recruited macrophages. LXA\n                      <jats:sub>4<\/jats:sub>\n                      improved antioxidant parameters [reduced glutathione (GSH) and 2,2-azino-bis 3-ethylbenzothiazoline-6-sulfonate (ABTS) levels, nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and Nrf2 protein expression], reducing reactive oxygen species (ROS) fluorescent detection induced by TiO2 in synovial fluid leukocytes. We observed an increase of lipoxin receptor (ALX\/FPR2) in transient receptor potential cation channel subfamily V member 1 (TRPV1)\n                      <jats:sup>+<\/jats:sup>\n                      DRG nociceptive neurons upon TiO\n                      <jats:sub>2<\/jats:sub>\n                      inflammation. LXA\n                      <jats:sub>4<\/jats:sub>\n                      reduced TiO\n                      <jats:sub>2<\/jats:sub>\n                      \u2010induced TRPV1 mRNA expression and protein detection, as well TRPV1 co-staining with p-NF\u03baB, indicating reduction of neuronal activation. LXA\n                      <jats:sub>4<\/jats:sub>\n                      down-modulated neuronal activation and response to capsaicin (a TRPV1 agonist) and AITC [a transient receptor potential ankyrin 1 (TRPA1) agonist] of DRG neurons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      LXA\n                      <jats:sub>4<\/jats:sub>\n                      might target recruited leukocytes and primary afferent nociceptive neurons to exert analgesic and anti-inflammatory activities in a model resembling what is observed in patients with prosthesis inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2023.949407","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T04:26:28Z","timestamp":1686716788000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Therapeutic activity of lipoxin A4 in TiO2-induced arthritis in mice: NF-\u03baB and Nrf2 in synovial fluid leukocytes and neuronal TRPV1 mechanisms"],"prefix":"10.3389","volume":"14","author":[{"given":"Telma","family":"Saraiva-Santos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago H.","family":"Zaninelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00edlia F.","family":"Manchope","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketlem 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