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Updated: Apr 18, 2026
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Published on: May 21, 2018
Modulation of Inflammasome Activity by miR-197-3p in Familial Mediterranean Fever Mouse Macrophages
Yeliz Z Akkaya-Ulum1, Basak Sen1, Tayfun Hilmi Akbaba1
1Department of Medical Biology, Hacettepe University Faculty of Medicine, Ankara, Türkiye.
Background/Aims:
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.
Materials And Methods:
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.
Results:
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.
Conclusion:
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.
Insights
MicroRNA-197-3p may regulate inflammation in familial Mediterranean fever (FMF) by specifically affecting pyrin inflammasome activation in macrophages. Further research is needed to confirm its role in FMF pathogenesis.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Familial Mediterranean fever (FMF) is an inflammasomopathy linked to MEFV gene mutations and pyrin inflammasome activity.
- Clinical variability in FMF suggests epigenetic factors, like microRNAs (miRNAs), play a regulatory role.
- miR-197-3p was previously identified as an inflammatory signaling regulator targeting IL1R1.
Purpose of the Study:
- To investigate the functional role of miR-197-3p in pyrin inflammasome activation and priming.
- To examine miR-197-3p's influence in macrophages from a mouse model of FMF.
Main Methods:
- Bone marrow-derived macrophages (BMDMs) from MefvV726A/V726A mice were transfected with miR-197-3p mimics.
- Inflammasome activation was induced via specific activators and Toll-like receptor (TLR) agonists targeting pyrin, AIM2, and NLRP3 pathways.
- Interleukin-1β (IL-1β) secretion and pro-IL-1β expression were measured.
Main Results:
- Overexpression of miR-197-3p significantly reduced IL-1β secretion specifically upon pyrin inflammasome activation.
- Inflammasome pathway responses other than pyrin were largely unaffected by miR-197-3p.
- miR-197-3p overexpression decreased pro-IL-1β expression following TLR2 stimulation.
Conclusions:
- miR-197-3p appears to preferentially modulate pyrin inflammasome-mediated inflammatory responses in FMF macrophages.
- The findings support a potential regulatory role for miR-197-3p in FMF-associated inflammation.
- Further mechanistic and in vivo studies are warranted to elucidate the precise role of miR-197-3p in FMF.
