PMID- 32886146 OWN - NLM STAT- MEDLINE DCOM- 20201130 LR - 20201217 IS - 1420-908X (Electronic) IS - 1023-3830 (Linking) VI - 69 IP - 12 DP - 2020 Dec TI - IL-33 enhances macrophage release of IL-1beta and promotes pain and inflammation in gouty arthritis. PG - 1271-1282 LID - 10.1007/s00011-020-01399-x [doi] AB - 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-1beta and superoxide anion levels. In macrophages, IL-33 enhanced the release of IL-1beta and TNF-alpha, 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. FAU - Fattori, Victor AU - Fattori V AD - Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Brazil. FAU - Staurengo-Ferrari, Larissa AU - Staurengo-Ferrari L AD - Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Brazil. FAU - Zaninelli, Tiago H AU - Zaninelli TH AD - Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Brazil. FAU - Casagrande, Rubia AU - Casagrande R AD - Department of Pharmaceutical Science, Londrina State University, Londrina, Brazil. FAU - Oliveira, Rene D AU - Oliveira RD AD - Division of Clinical Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Louzada-Junior, Paulo AU - Louzada-Junior P AD - Division of Clinical Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Cunha, Thiago M AU - Cunha TM AD - Department of Pharmacology, Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Alves-Filho, Jose C AU - Alves-Filho JC AD - Department of Pharmacology, Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Teixeira, Mauro M AU - Teixeira MM AD - Departamento de Bioquimica e Imunologia, Instituto de Ciencias Biologicas (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Cunha, Fernando Q AU - Cunha FQ AD - Department of Pharmacology, Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Amaral, Flavio A AU - Amaral FA AD - Departamento de Bioquimica e Imunologia, Instituto de Ciencias Biologicas (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Verri, Waldiceu A Jr AU - Verri WA Jr AUID- ORCID: 0000-0003-2756-9283 AD - Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina, Brazil. waldiceujr@yahoo.com.br. AD - Departamento de Ciencias Patologicas, Centro de Ciencias Biologicas, 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. LA - eng GR - agreement 041/2017, protocol 48.095/Department of Science and Technology from the Science, Technology and Strategic Inputs Secretariat of the Ministry of Health (Decit/SCTIE/MS, Brazil) intermediated by CNPq with support of Araucaria Foundation and State Health Secretariat, Parana (SESA-PR,/ GR - Grant agreements 01.12.0294.00 and 01.13.0049.00/Funding Authority for Studies and Projects and State Secretariat of Science, Technology and Higher Education (MCTI/FINEP/CT-INFRA-PROINFRA, Brazil)/ GR - agreement 014/2017, protocol 46.843/Programa de Apoio a Grupos de Excelencia (PRONEX) grant supported by SETI/Araucaria Foundation and MCTI/CNPq; and Parana State Government/ GR - 001/Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/ GR - Center for Research in Inflammatory Disease under grant agreement 2013/08216-2/Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/ PT - Journal Article DEP - 20200904 PL - Switzerland TA - Inflamm Res JT - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JID - 9508160 RN - 0 (IL1B protein, mouse) RN - 0 (IL33 protein, human) RN - 0 (Il1rl1 protein, mouse) RN - 0 (Interleukin-1 Receptor-Like 1 Protein) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-33) RN - 11062-77-4 (Superoxides) RN - 268B43MJ25 (Uric Acid) RN - EC 1.11.1.7 (Peroxidase) SB - IM MH - Animals MH - Arthritis, Gouty/chemically induced/metabolism/*pathology MH - Female MH - Humans MH - Inflammation/*chemically induced/psychology MH - Interleukin-1 Receptor-Like 1 Protein/genetics MH - Interleukin-1beta/*metabolism MH - Interleukin-33/*pharmacology MH - Macrophages/drug effects/*metabolism MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Knockout MH - Middle Aged MH - Neutrophil Infiltration/drug effects MH - Pain/*chemically induced/psychology MH - Peroxidase/metabolism MH - Superoxides/metabolism MH - Synovial Membrane/pathology MH - Uric Acid OTO - NOTNLM OT - Gout flares OT - IL-33 OT - Joint pain OT - Macrophages OT - ST2 EDAT- 2020/09/05 06:00 MHDA- 2020/12/01 06:00 CRDT- 2020/09/05 06:00 PHST- 2020/05/21 00:00 [received] PHST- 2020/08/30 00:00 [accepted] PHST- 2020/07/29 00:00 [revised] PHST- 2020/09/05 06:00 [pubmed] PHST- 2020/12/01 06:00 [medline] PHST- 2020/09/05 06:00 [entrez] AID - 10.1007/s00011-020-01399-x [pii] AID - 10.1007/s00011-020-01399-x [doi] PST - ppublish SO - Inflamm Res. 2020 Dec;69(12):1271-1282. doi: 10.1007/s00011-020-01399-x. Epub 2020 Sep 4.