Knockdown of NFIL3 modulates the AMPK pathway to suppress excessive cell proliferation, inflammation, and migration in rheumatoid arthritis

Background

Rheumatoid arthritis (RA) is one autoimmune disease that badly influences the lives of humans. Nuclear factor interleukin 3 (NFIL3) has been elucidated to join into the progression of diversiform diseases. According to a recent report, NFIL3 expression levels are increased in the peripheral blood and synovial tissues of individuals with RA. However, the detailed regulatory impacts of NFIL3 and associated pathways in RA progression need more investigations.

Methods

The mRNA and protein expressions were tested through RT-qPCR and western blot. The cell proliferation was evaluated through CCK-8 and EdU assay. The cell apoptosis was measured through flow cytometry. The levels of TNF-α, IL-6, and IL-8 were assessed through ELISA. The cell migration and invasion were tested through Transwell assay.

Results

In this study, NFIL3 exhibited higher expression in RA fibroblast-like synoviocytes (interleukin-1β [IL-1β]-triggered MH7A cell model). In addition, knockdown of NFIL3 repressed the growth of IL-1β-mediated MH7A cells. It was also demonstrated that suppressing NFIL3 resulted in reduced inflammatory reactions in IL-1β-mediated MH7A cells. Suppression of NFIL3 alleviated cell migration and invasion in the RA cell model. Ultimately, it was demonstrated that NFIL3 retarded the AMPK/mTOR pathway.

Conclusion

This study demonstrated that the inhibition of NFIL3 effectively controlled the AMPK/mTOR pathway, thereby suppressing the overactive proliferation, inflammation, and migration of fibroblast-like synoviocytes in human RA. This discovery implied that NFIL3 can be a serviceable biomarker for RA therapy.