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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.
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http://dx.doi.org/10.1042/CS20201348 | DOI Listing |
Front Immunol
December 2024
Department of Gastrointestinal Surgery, Huadu District People's Hospital, Guangzhou, China.
Gut immunity is essential for maintaining intestinal health. Recent studies have identified that intracellular liquid-liquid phase separation (LLPS) may play a significant role in regulating gut immunity, however, the underlying mechanisms remain unclear. LLPS refers to droplet condensates formed through intracellular molecular interactions, which are crucial for the formation of membraneless organelles and biomolecules.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Dermatology, First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Background: Psoriatic arthritis (PSA) is an inflammatory joint disease associated with psoriasis (PSO) that can be easily missed. Existing PSA screening tools ignore objective serologic indicators. The aim of this study was to develop a disease screening model and the Psoriatic Arthritis Inflammation Index (PSAII) based on serologic data to enhance the efficiency of PSA screening.
View Article and Find Full Text PDFFront Immunol
December 2024
Aix Marseille University, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille-Luminy (CIML), Marseille, France.
Hematopoietic stem cells (HSCs) are a rare, long-lived and multipotent population that give rise to majority of blood cells and some tissue-resident immune cells. There is growing evidence that inflammatory stimuli can trigger persistent reprogramming in HSCs that enhances or inhibits the cellular functions of these HSCs and their progeny in response to subsequent infections. This newly discovered property makes HSCs a reservoir for innate immune memory.
View Article and Find Full Text PDFFront Microbiol
December 2024
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Introduction: Protein acetylation is an extensively investigated post-translational modification (PTM). In addition to lysine acetylation, three new types of lysine acylations characterized by the presence of an acidic carboxylic group have been recently identified and validated. These included lysine malonylation (Kmal), lysine succinylation (Ksucc) and lysine glutarylation (Kglu).
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
December 2024
Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China.
Background: The association between the triglyceride-glucose (TyG) index and mortality in the general population remains controversial, with inconsistent findings across studies.
Objective: This study aims to investigate the relationship between the TyG index and mortality in the U.S.
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