Macrophage inflammatory state in Type 1 diabetes: triggered by NLRP3/iNOS pathway and attenuated by docosahexaenoic acid
Davanso MR, Crisma AR, Braga TT, Masi LN, do Amaral CL, Leal VNC, de Lima DS, Patente TA, Barbuto JA, Corrêa-Giannella ML, Lauterbach M, Kolbe CC, Latz E, Camara NOS, Pontillo A, Curi R
Clinical science (London, England : 1979) · 38 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Funding not disclosed
Publication
- Published
- 2020-12-02 · Clin Sci (Lond) · vol. 135 · issue 1 · pp. 19–34
- Publisher
- Portland Press
- Cited
- 52 citations · more than 89% of similar papers · 2.3× the field average
- References
- 91 works
- Access
- Open access (hybrid journal) · CC-BY
- Research areas
- Inflammasome and immune disorders · Fatty Acid Research and Health · Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Keywords
- Proinflammatory cytokine, Endocrinology, Docosahexaenoic acid, Inflammasome, Internal medicine, Insulitis, Inflammation, Chemokine, Chemistry, Nod, Medicine, Immunology, Diabetes mellitus, Biochemistry, Polyunsaturated fatty acid, Fatty acid
- MeSH
- cells, cultured, macrophages, peritoneal, animals, mice, inbred c57bl, mice, inbred nod, mice, knockout, humans, mice, diabetes mellitus, experimental, diabetes mellitus, type 1, inflammation, streptozocin, docosahexaenoic acids, anti-inflammatory agents, inflammation mediators, cytokines, signal transduction, macrophage activation, pregnancy, adult, middle aged, female, male, nitric oxide synthase type ii, nlr family, pyrin domain-containing 3 protein
16 authors
From DE, BR
- Mariana Rodrigues DavansoUniversity of Bonn; Universidade de São Paulo; University Hospital Bonn
- Amanda Rabello CrismaUniversidade de São Paulo; Universidade Federal do Paraná
- Tárcio Teodoro BragaUniversity of Bonn; University Hospital Bonn; Universidade Federal do Paraná
- Laureane Nunes MasiUniversidade de São Paulo; Universidade Cruzeiro do Sul
- Cátia Lira do AmaralUniversidade Estadual de Goiás
- Vinícius Nunes Cordeiro LealUniversidade de São Paulo
Abstract
Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease characterized by insulin-producing pancreatic β-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-1β 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-1β 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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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