Therapeutic activity of lipoxin A4 in TiO2-induced arthritis in mice: NF-κB and Nrf2 in synovial fluid leukocytes and neuronal TRPV1 mechanisms
BackgroundLipoxin A4 (LXA4) has anti-inflammatory and pro-resolutive roles in inflammation. We evaluated the effects and mechanisms of action of LXA4 in titanium dioxide (TiO2) arthritis, a model of prosthesis-induced joint inflammation and pain.MethodsMice were stimulated with TiO2 (3mg) in the kne...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.949407/full |
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| author | Telma Saraiva-Santos Telma Saraiva-Santos Tiago H. Zaninelli Tiago H. Zaninelli Tiago H. Zaninelli Marília F. Manchope Ketlem C. Andrade Camila R. Ferraz Mariana M. Bertozzi Nayara A. Artero Anelise Franciosi Stephanie Badaro-Garcia Larissa Staurengo-Ferrari Sergio M. Borghi Sergio M. Borghi Graziela S. Ceravolo Avacir Casanova Andrello Janaína Menezes Zanoveli Michael S. Rogers Rubia Casagrande Felipe A. Pinho-Ribeiro Waldiceu A. Verri |
| author_facet | Telma Saraiva-Santos Telma Saraiva-Santos Tiago H. Zaninelli Tiago H. Zaninelli Tiago H. Zaninelli Marília F. Manchope Ketlem C. Andrade Camila R. Ferraz Mariana M. Bertozzi Nayara A. Artero Anelise Franciosi Stephanie Badaro-Garcia Larissa Staurengo-Ferrari Sergio M. Borghi Sergio M. Borghi Graziela S. Ceravolo Avacir Casanova Andrello Janaína Menezes Zanoveli Michael S. Rogers Rubia Casagrande Felipe A. Pinho-Ribeiro Waldiceu A. Verri |
| author_sort | Telma Saraiva-Santos |
| collection | DOAJ |
| description | BackgroundLipoxin A4 (LXA4) has anti-inflammatory and pro-resolutive roles in inflammation. We evaluated the effects and mechanisms of action of LXA4 in titanium dioxide (TiO2) arthritis, a model of prosthesis-induced joint inflammation and pain.MethodsMice were stimulated with TiO2 (3mg) in the knee joint followed by LXA4 (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 LXA4in vivo.ResultsLXA4 reduced mechanical and thermal hyperalgesia, histopathological damage, edema, and recruitment of leukocytes without liver, kidney, or stomach toxicity. LXA4 reduced leukocyte migration and modulated cytokine production. These effects were explained by reduced nuclear factor kappa B (NFκB) activation in recruited macrophages. LXA4 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)+ DRG nociceptive neurons upon TiO2 inflammation. LXA4 reduced TiO2‐induced TRPV1 mRNA expression and protein detection, as well TRPV1 co-staining with p-NFκB, indicating reduction of neuronal activation. LXA4 down-modulated neuronal activation and response to capsaicin (a TRPV1 agonist) and AITC [a transient receptor potential ankyrin 1 (TRPA1) agonist] of DRG neurons.ConclusionLXA4 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. |
| first_indexed | 2024-03-13T05:35:51Z |
| format | Article |
| id | doaj.art-bcd1d34c704c4929903bb0223edab626 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T05:35:51Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-bcd1d34c704c4929903bb0223edab6262023-06-14T08:26:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.949407949407Therapeutic activity of lipoxin A4 in TiO2-induced arthritis in mice: NF-κB and Nrf2 in synovial fluid leukocytes and neuronal TRPV1 mechanismsTelma Saraiva-Santos0Telma Saraiva-Santos1Tiago H. Zaninelli2Tiago H. Zaninelli3Tiago H. Zaninelli4Marília F. Manchope5Ketlem C. Andrade6Camila R. Ferraz7Mariana M. Bertozzi8Nayara A. Artero9Anelise Franciosi10Stephanie Badaro-Garcia11Larissa Staurengo-Ferrari12Sergio M. Borghi13Sergio M. Borghi14Graziela S. Ceravolo15Avacir Casanova Andrello16Janaína Menezes Zanoveli17Michael S. Rogers18Rubia Casagrande19Felipe A. Pinho-Ribeiro20Waldiceu A. Verri21Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Paraná, BrazilDivision of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United StatesLaboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Paraná, BrazilDivision of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United StatesVascular Biology Program, Department of Surgery, Boston Children's Hospital-Harvard Medical School, Boston, MA, United StatesLaboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Paraná, BrazilLaboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Paraná, BrazilLaboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Paraná, BrazilLaboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Paraná, BrazilLaboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Paraná, BrazilLaboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Paraná, BrazilLaboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Paraná, BrazilLaboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Paraná, BrazilLaboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Paraná, BrazilCenter for Research in Health Sciences, University of Northern Paraná, Londrina, Paraná, BrazilDepartment of Physiological Sciences, Center for Biological Sciences, Londrina State University, Londrina, Paraná, BrazilDepartment of Physics, Londrina State University, Londrina, Paraná, BrazilDepartment of Pharmacology, Biological Sciences Sector, Federal University of Parana, Curitiba, Parana, BrazilVascular Biology Program, Department of Surgery, Boston Children's Hospital-Harvard Medical School, Boston, MA, United StatesDepartment of Pharmaceutical Sciences, Centre of Health Sciences, Londrina State University, Londrina, Paraná, BrazilDivision of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United StatesLaboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Paraná, BrazilBackgroundLipoxin A4 (LXA4) has anti-inflammatory and pro-resolutive roles in inflammation. We evaluated the effects and mechanisms of action of LXA4 in titanium dioxide (TiO2) arthritis, a model of prosthesis-induced joint inflammation and pain.MethodsMice were stimulated with TiO2 (3mg) in the knee joint followed by LXA4 (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 LXA4in vivo.ResultsLXA4 reduced mechanical and thermal hyperalgesia, histopathological damage, edema, and recruitment of leukocytes without liver, kidney, or stomach toxicity. LXA4 reduced leukocyte migration and modulated cytokine production. These effects were explained by reduced nuclear factor kappa B (NFκB) activation in recruited macrophages. LXA4 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)+ DRG nociceptive neurons upon TiO2 inflammation. LXA4 reduced TiO2‐induced TRPV1 mRNA expression and protein detection, as well TRPV1 co-staining with p-NFκB, indicating reduction of neuronal activation. LXA4 down-modulated neuronal activation and response to capsaicin (a TRPV1 agonist) and AITC [a transient receptor potential ankyrin 1 (TRPA1) agonist] of DRG neurons.ConclusionLXA4 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.949407/fulllipoxin A4TiO2ALX/FPR2inflammationTRPV1ROS |
| spellingShingle | Telma Saraiva-Santos Telma Saraiva-Santos Tiago H. Zaninelli Tiago H. Zaninelli Tiago H. Zaninelli Marília F. Manchope Ketlem C. Andrade Camila R. Ferraz Mariana M. Bertozzi Nayara A. Artero Anelise Franciosi Stephanie Badaro-Garcia Larissa Staurengo-Ferrari Sergio M. Borghi Sergio M. Borghi Graziela S. Ceravolo Avacir Casanova Andrello Janaína Menezes Zanoveli Michael S. Rogers Rubia Casagrande Felipe A. Pinho-Ribeiro Waldiceu A. Verri Therapeutic activity of lipoxin A4 in TiO2-induced arthritis in mice: NF-κB and Nrf2 in synovial fluid leukocytes and neuronal TRPV1 mechanisms Frontiers in Immunology lipoxin A4 TiO2 ALX/FPR2 inflammation TRPV1 ROS |
| title | Therapeutic activity of lipoxin A4 in TiO2-induced arthritis in mice: NF-κB and Nrf2 in synovial fluid leukocytes and neuronal TRPV1 mechanisms |
| title_full | Therapeutic activity of lipoxin A4 in TiO2-induced arthritis in mice: NF-κB and Nrf2 in synovial fluid leukocytes and neuronal TRPV1 mechanisms |
| title_fullStr | Therapeutic activity of lipoxin A4 in TiO2-induced arthritis in mice: NF-κB and Nrf2 in synovial fluid leukocytes and neuronal TRPV1 mechanisms |
| title_full_unstemmed | Therapeutic activity of lipoxin A4 in TiO2-induced arthritis in mice: NF-κB and Nrf2 in synovial fluid leukocytes and neuronal TRPV1 mechanisms |
| title_short | Therapeutic activity of lipoxin A4 in TiO2-induced arthritis in mice: NF-κB and Nrf2 in synovial fluid leukocytes and neuronal TRPV1 mechanisms |
| title_sort | therapeutic activity of lipoxin a4 in tio2 induced arthritis in mice nf κb and nrf2 in synovial fluid leukocytes and neuronal trpv1 mechanisms |
| topic | lipoxin A4 TiO2 ALX/FPR2 inflammation TRPV1 ROS |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.949407/full |
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