Modulation of Inflammasome Activity by miR-197-3p in Familial Mediterranean Fever Mouse Macrophages.

Familial Mediterranean fever (FMF) is an autosomal recessive inflammasomopathy caused by mutations in the MEditerranean FeVer (MEFV) gene and is characterized by recurrent inflammatory attacks largely associated with pyrin inflammasome activity. Although FMF is a monogenic disease, clinical heterogeneity suggests the contribution of additional regulatory mechanisms, including epigenetic factors such as microRNAs (miRNAs). Previous studies identified miR-197-3p as a regulator of inflammatory signaling by targeting IL1R1. The objective of this study was to investigate the functional role of miR-197-3p in pyrin inflammasome activation and priming mechanisms in macrophages derived from an FMF knock-in mouse model. Bone marrow-derived macrophages (BMDMs) from MefvV726A/V726A mice were transfected with pre-miR-197-3p or a mimic control. Following transfection, inflammasome priming and activation were induced using specific inflammasome activators and Toll-like receptor (TLR) agonists targeting pyrin, AIM2, and NOD-like receptor protein 3 pathways. Interleukin-1β (IL-1β) secretion and pro-IL-1β expression were subsequently assessed. Overexpression of miR-197-3p significantly reduced IL-1β secretion following just pyrin inflammasome activation, while responses mediated by other inflammasome pathways were largely preserved. In addition, miR- 197-3p overexpression was associated with decreased pro-IL-1β expression in response to TLR2 stimulation. These findings suggest that miR-197-3p may preferentially influence pyrin inflammasome-related inflammatory responses in FMF macrophages. While the present data do not establish a direct mechanistic interaction, they support a potential regulatory role for miR-197-3p in FMF-associated inflammation and provide a basis for future mechanistic and in vivo studies. Cite this article as: Ulum YZA, Sen B, Akbaba TH, Peynircioglu BB. Modulation of inflammasome activity by miR-197-3p in familial Mediterranean fever mouse macrophages. Arch Rheumatol. 2026;41(2):144-152.