Hypomethylation of IL1RN and NFKB1 genes is linked to the dysbalance in IL1β/IL-1Ra axis in female patients with type 2 diabetes mellitus.

摘要: Inflammation has received considerable attention in the pathogenesis of type 2 diabetes mellitus (T2DM). Supporting this concept, enhanced expression interleukin (IL)-1β and increased infiltration macrophages are observed pancreatic islets patients with T2DM. Although IL-1 receptor antagonist (IL-1Ra) plays a major role controlling IL-1β-mediated inflammation, its counteraction effects epigenetic alterations T2DM less studied. Thus, we aimed to analyze DNA methylation status IL1RN, RELA (p65) NFKB1 (p50) genes peripheral blood mononuclear cells (PBMCs) from treated (n = 35) age-/sex- matched healthy controls 31). Production IL-1β IL-1Ra was analyzed plasma supernatants LPS-induced PBMCs. Immunomodulatory were studied on THP-1 cells. Average level IL1RN gene promoters significantly decreased comparison (P< 0.05), which associated 0.001) (P 0.039) levels patients. Negative association between average female Methylation negatively correlated positively LPS-stimulated PBMCs failed raise production, while females production unstimulated 0.001). Taken together, findings suggest that hypomethylation may promote IL-1β/IL-1Ra regulate chronic inflammation Further studies necessary elucidate causal direction these associations potential anti-inflammatory processes