TNF-α-induced miR-155 regulates IL-6 signaling in rheumatoid synovial fibroblasts.

BACKGROUND

MicroRNAs (miRNAs) are important regulators of a variety of inflammatory mediators. The present study was undertaken to elucidate the role of miRNAs in the rheumatoid cytokine network.

METHODS

We analyzed miRNA expression in rheumatoid synovial fibroblasts (RASFs). miRNA array-based screening was used to identify miRNAs differentially expressed between tumor necrosis factor-α (TNF-α)-activated RASFs and untreated RASFs. Transfection of RASFs with miR-155 was used to analyze the function of miR-155. Real-time polymerase chain reaction (PCR) was used to measure the levels of miR-155 in RASFs.

RESULTS

miRNA microarray analysis revealed that miR-155-5p was the most highly induced miRNA in TNF-α-stimulated RASFs. TNF-α-induced miR-155 expression in RASFs was time-dependent and TNFα dose-dependent, whereas, IL-6 stimulation did not affect miR-155 expression in RASFs. Transfection of miR-155 mimics into RASFs resulted in the decrease JAK2/STAT3 phosphorylation in IL-6-treated RASFs.

CONCLUSIONS

The current results demonstrate that TNF-α modulated miRNA expressions in RASFs. Our data showed that miR-155, which is highly induced by TNF-α stimulation, inhibits IL-6-mediated JAK2/STAT3 activation in RASFs. These findings suggest that miR-155 contributes to the cross-regulation between TNF-α and IL-6-mediated inflammatory pathways in RA.