TNF-α induces expression of the circadian clock gene Bmal1 via dual calcium-dependent pathways in rheumatoid synovial cells

Tumor necrosis factor (TNF)-α induces the over-expression of Bmal1 in rheumatoid synovial cells through calcium-dependent pathways.

• TNF-α enhances the oscillation of Rorα, a transcriptional activator, contributing to increased levels of Bmal1.
• The oscillation phase of Rev-erbα remains unaffected by TNF-α, indicating a specific regulatory mechanism.
• Inhibition of calcium influx using BAPTA-AM cancels the TNF-α-mediated up-regulation of Rorα but does not affect Bmal1 expression.
• TNF-α suppresses Rev-erbα expression and the genes p300 and CBP in the absence of calcium influx.
• Inhibition of p300/CBP with C646 or silencing their expression negates the effects of TNF-α on Bmal1 and Rorα.

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