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The clock gene Bmal1 controls inflammatory mediators in rheumatoid arthritis fibroblast-like synoviocytes

Kenta Kaneshiro¹, Kanako Nakagawa¹, Hikari Tsukamoto¹

¹Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan.

Biochemical and Biophysical Research Communications

|December 3, 2023

Abstract

Object:

To clarify the involvement of clock genes in the production of inflammatory mediators from RA-FLS, we examined the role of Bmal1, one of the master clock genes.

Methods:

RA-FLSs were stimulated with IL-1β (0, 20 ng/mL), IL-6 (0, 20 ng/mL), IL-17 (0, 20 ng/mL), TNF-α (0, 20 ng/mL) or IFN-γ (0, 20 ng/mL) to examine the expression of Bmal1, MMP-3, CCL2, IL-6, IL-7 and IL-15 by qPCR and immunofluorescence staining. After silencing Bmal1, RA-FLSs were stimulated with IL-1β (0, 20 ng/mL), TNF-α (0, 20 ng/mL) or IFN-γ (0, 20 ng/mL) to examine the expressions of inflammatory mediators; MMP-3, CCL2, IL-6 and IL-15 by qPCR, ELISA and immunofluorescence staining.

Results:

Bmal1 expressions were increased by IL-1β, TNF-α and IFN-γ stimulations. Under stimulations with TNF-α, IL-1β, and IFN-γ, mRNA and protein expressions of MMP-3, CCL2 and IL-6 were suppressed by siBmal1.

Conclusion:

Results indicate that Bmal1 contributes the production of MMP-3, CCL2, and IL-6 from RA-FLS, implying Bmal1 is involved in the pathogenesis of RA by regulating the inflammation.

Keywords:

BMAL1 Clock gene Fibroblast-like synoviocyte Inflammatory mediators Rheumatoid arthritis

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