How three immune signals differently affect two related microRNAs in human eye support cells

Both miR-146a and miR-146b-5p are expressed in human retinal pigment epithelial cells and are significantly induced by proinflammatory cytokines.

• The expression of miR-146a and miR-146b-5p increased in response to the combination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β.
• Induction of miR-146a was found to be particularly dependent on IL-1β, while miR-146b-5p was more influenced by IFN-γ.
• Increased expression of these microRNAs was associated with heightened levels of proinflammatory transcripts, including CCL2, CCL5, CXCL9, CXCL10, and IL-6, and a decrease in HMOX1 transcripts.
• The activity of the MIR146B promoter was inhibited by JAK inhibitor 1, suggesting involvement of the JAK/STAT signaling pathway in its regulation.
• Transfection of RPE cells with miR-146a or miR-146b-5p mimics resulted in decreased levels of IRAK1 protein.

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