Icariin alleviates rheumatoid arthritis via regulating miR-223-3p/NLRP3 signalling axis

Abstract

Rheumatoid arthritis (RA) is considered to be a chronic autoimmune disease, pathogenesis of RA is complex and effective treatments for RA is still lacking. Previous studies found that microRNAs (miRNAs) play important roles in the pathogenesis of RA, and miR-223-3p is considered to be one of the possible biomarkers of RA. Recent studies have revealed that icariin alleviates RA in murine models, but the underlying mechanism needs to be further investigated. MiR-223-3p expression levels in fibroblast-like synoviocyte (RA-FLS) and patients with RA were quantified by qRT-PCR, cell proliferation was analyzed by CCK-8 and BrdU assay. Cell apoptosis was assessed by flow cytometry and western blotting. TNF-α, IL-1β and IL-6 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Dual luminescence-based reporter gene assay was conducted to confirm the possible interaction between miR-223-3p and NLRP3. Icariin inhibits proliferation and inflammation cytokines secretion, promotes apoptosis of RA-FLS cells and upregulated the expression of miR-223-3p. MiR-223-3p targets to 3’-UTR of NRLP3 and regulates its expression. MiR-223-3p inhibitor reversed the effect of icariin on RA-FLS cells function. Additionally, anti-RA activity of icariin was restored by NLRP3 inhibitor MCC950 in miR-223-3p knockdown RA-FLS cells. Icariin inhibits proliferation and inflammation, promotes apoptosis of RA-FLS cells by regulating miR-223-3p/NLRP3 signalling, which may serve as a potential therapeutic target to alleviate RA.

Keywords:

• Icariin
• rheumatoid arthritis
• MiR-223-3p
• NLRP3
• chronic autoimmune disease

Acknowledgements

Thanks to the members of our laboratory for their contributions.

Ethics approval

Not applicable. This article does not contain any studies with human participants or animals performed by any of the authors.

Author contributions

Zhi-Ming Wu: methodology, software, writing – original draft preparation, writing – reviewing and editing; Jun Luo: conceptualization, investigation; Xiao-Dong Shi: visualization, investigation; Shao-Xin Zhang: data curation; Xiao-Bo Zhu: visualization; Jian Guo: Conceptualization, supervision.

Disclosure statement

The authors report no conflict of interest.

Data availability statement

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.