{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:45:18Z","timestamp":1790401518809,"version":"4.1.0"},"reference-count":89,"publisher":"Portland Press Ltd.","issue":"1","license":[{"start":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:00:00Z","timestamp":1606867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease characterized by insulin-producing pancreatic \u03b2-cell destruction and hyperglycemia. While monocytes and NOD-like receptor family-pyrin domain containing 3 (NLRP3) are associated with T1D onset and development, the specific receptors and factors involved in NLRP3 inflammasome activation remain unknown. Herein, we evaluated the inflammatory state of resident peritoneal macrophages (PMs) from genetically modified non-obese diabetic (NOD), NLRP3-KO, wild-type (WT) mice and in peripheral blood mononuclear cells (PBMCs) from human T1D patients. We also assessed the effect of docosahexaenoic acid (DHA) on the inflammatory status. Macrophages from STZ-induced T1D mice exhibited increased inflammatory cytokine\/chemokine levels, nitric oxide (NO) secretion, NLRP3 and iNOS protein levels, and augmented glycolytic activity compared to control animals. In PMs from NOD and STZ-induced T1D mice, DHA reduced NO production and attenuated the inflammatory state. Furthermore, iNOS and IL-1\u03b2 protein expression levels and NO production were lower in the PMs from diabetic NLRP3-KO mice than from WT mice. We also observed increased IL-1\u03b2 secretion in PBMCs from T1D patients and immortalized murine macrophages treated with advanced glycation end products and palmitic acid. The present study demonstrated that the resident PMs are in a proinflammatory state characterized by increased NLRP3\/iNOS pathway-mediated NO production, up-regulated proinflammatory cytokine\/chemokine receptor expression and altered glycolytic activity. Notably, ex vivo treatment with DHA reverted the diabetes-induced changes and attenuated the macrophage inflammatory state. It is plausible that DHA supplementation could be employed as adjuvant therapy for treating individuals with T1D.<\/jats:p>","DOI":"10.1042\/cs20201348","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T12:56:05Z","timestamp":1606913765000},"page":"19-34","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Macrophage inflammatory state in Type 1 diabetes: triggered by NLRP3\/iNOS pathway and attenuated by docosahexaenoic acid"],"prefix":"10.1042","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1936-320X","authenticated-orcid":false,"given":"Mariana\u00a0Rodrigues","family":"Davanso","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil"},{"name":"Laboratory of Immunogenetics, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil"},{"name":"Institute of Innate Immunity, University Hospital, University of Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda\u00a0Rabello","family":"Crisma","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil"},{"name":"Laboratory of Physiology and Cell Signalling, Department of Clinical Analyses, Federal University of Paran\u00e1, Curitiba, Paran\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2989-1076","authenticated-orcid":false,"given":"T\u00e1rcio\u00a0Teodoro","family":"Braga","sequence":"additional","affiliation":[{"name":"Institute of Innate Immunity, University Hospital, University of Bonn, Bonn, Germany"},{"name":"Department of Basic Pathology, Federal University of Parana, Curitiba, Parana, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9472-7304","authenticated-orcid":false,"given":"Laureane\u00a0Nunes","family":"Masi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil"},{"name":"Interdisciplinary Post-graduate Program in Health Sciences, Cruzeiro of Sul University, Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e1tia\u00a0Lira","family":"do Amaral","sequence":"additional","affiliation":[{"name":"Campus of Exact Sciences and Technology, State University of Goias, Anapolis, Goias, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vin\u00edcius Nunes\u00a0Cordeiro","family":"Leal","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dh\u00eamerson\u00a0Souza","family":"de Lima","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago\u00a0Andrade","family":"Patente","sequence":"additional","affiliation":[{"name":"Laboratory of Tumour Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9\u00a0Alexandre","family":"Barbuto","sequence":"additional","affiliation":[{"name":"Laboratory of Tumour Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria\u00a0L.","family":"Corr\u00eaa-Giannella","sequence":"additional","affiliation":[{"name":"Laboratory of Carbohydrates and Radioimmunoassay, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil"},{"name":"Post-graduation Program of Medicine, UNINOVE, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Lauterbach","sequence":"additional","affiliation":[{"name":"Institute of Innate Immunity, University Hospital, University of Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl\u00a0Christian","family":"Kolbe","sequence":"additional","affiliation":[{"name":"Institute of Innate Immunity, University Hospital, University of Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eicke","family":"Latz","sequence":"additional","affiliation":[{"name":"Institute of Innate Immunity, University Hospital, University of Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5436-1248","authenticated-orcid":false,"given":"Niels Olsen\u00a0Saraiva","family":"Camara","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology of Transplantation, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Pontillo","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Curi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil"},{"name":"Interdisciplinary Post-graduate Program in Health Sciences, Cruzeiro of Sul University, Sao Paulo, Sao Paulo, Brazil"},{"name":"Butantan Institute, Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,1,5]]},"reference":[{"key":"2021113011175656700_B1","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1038\/414792a","article-title":"beta-Cell death during progression to diabetes","volume":"414","author":"Mathis","year":"2001","journal-title":"Nature"},{"key":"2021113011175656700_B2","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/S0092-8674(00)81106-X","article-title":"Insulin-dependent diabetes mellitus","volume":"85","author":"Tisch","year":"1996","journal-title":"Cell"},{"key":"2021113011175656700_B3","doi-asserted-by":"publisher","first-page":"2797","DOI":"10.2337\/diabetes.53.11.2797","article-title":"Fas deficiency prevents type 1 diabetes by inducing 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