Victor Fattori1, Larissa Staurengo-Ferrari1, Tiago H Zaninelli1, Rubia Casagrande2, Rene D Oliveira3, Paulo Louzada-Junior3, Thiago M Cunha4, Jose C Alves-Filho4, Mauro M Teixeira5, Fernando Q Cunha4, Flavio A Amaral5, Waldiceu A Verri6,7. 1. Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Brazil. 2. Department of Pharmaceutical Science, Londrina State University, Londrina, Brazil. 3. Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. 4. Department of Pharmacology, Center for Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. 5. Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. 6. Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Brazil. waldiceujr@yahoo.com.br. 7. Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid, PR 445, KM 380, PO Box 10.011, Londrina, Parana, 86057-970, Brazil. waldiceujr@yahoo.com.br.
Abstract
OBJECTIVE: To investigate the role of IL-33 in gouty arthritis. MATERIAL: 174 Balb/c (wild-type) and 54 ST2-/- mice were used in this study. In vitro experiments were conducted in bone marrow-derived macrophages (BMDMs). Synovial fluid samples from gouty arthritis (n = 7) and osteoarthritis (n = 8) hospital patients were used to measure IL-33 and sST2 levels. METHODS: Gout was induced by injection of monosodium urate (MSU) crystals in the knee joint of mice. Pain was determined using the electronic von Frey and static weight bearing. Neutrophil recruitment was determined by H&E staining, Rosenfeld staining slides, and MPO activity. ELISA was used for cytokine and sST2 measurement. The priming effect of IL-33 was determined in BMDM. RESULTS: Synovial fluid of gout patients showed higher IL-33 levels and neutrophil counts than osteoarthritis patients. In mice, the absence of ST2 prevented mechanical pain, knee joint edema, neutrophil recruitment to the knee joint, and lowered IL-1β and superoxide anion levels. In macrophages, IL-33 enhanced the release of IL-1β and TNF-α, and BMDMs from ST2-/- showed reduced levels of these cytokines after stimulus with MSU crystals. CONCLUSION: IL-33 mediates gout pain and inflammation by boosting macrophages production of cytokines upon MSU crystals stimulus.
OBJECTIVE: To investigate the role of IL-33 in gouty arthritis. MATERIAL: 174 Balb/c (wild-type) and 54 ST2-/- mice were used in this study. In vitro experiments were conducted in bone marrow-derived macrophages (BMDMs). Synovial fluid samples from gouty arthritis (n = 7) and osteoarthritis (n = 8) hospital patients were used to measure IL-33 and sST2 levels. METHODS:Gout was induced by injection of monosodium urate (MSU) crystals in the knee joint of mice. Pain was determined using the electronic von Frey and static weight bearing. Neutrophil recruitment was determined by H&E staining, Rosenfeld staining slides, and MPO activity. ELISA was used for cytokine and sST2 measurement. The priming effect of IL-33 was determined in BMDM. RESULTS: Synovial fluid of goutpatients showed higher IL-33 levels and neutrophil counts than osteoarthritispatients. In mice, the absence of ST2 prevented mechanical pain, knee joint edema, neutrophil recruitment to the knee joint, and lowered IL-1β and superoxide anion levels. In macrophages, IL-33 enhanced the release of IL-1β and TNF-α, and BMDMs from ST2-/- showed reduced levels of these cytokines after stimulus with MSU crystals. CONCLUSION:IL-33 mediates gout pain and inflammation by boosting macrophages production of cytokines upon MSU crystals stimulus.
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