Figure 12. MicroRNA-146a and microRNA-146b-5p can potentially negatively regulate the inflammatory response of the retinal pigment epithelium. The schematic diagram shows that the retinal pigment epithelial (RPE) cells respond to the proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) by increasing the expression of inflammatory response genes. IL-1β and TNF-α regulate the gene expression by binding to specific cell surface receptors and thereby activating the nuclear factor (NF)-κB signaling pathway. Interleukin-1-receptor-associated kinase-1 (IRAK1) and TNF receptor associated factor 6 (TRAF6) are known modulators of the NF-κB pathway. IFN-γ alters gene expression by interacting with its cell surface receptors and then activating the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signal transduction pathway. The activation of NF-κB and JAK/STAT pathways by the proinflammatory cytokines can also cause an increase in the expression of miR-146a and miR-146b-5p in the RPE cells. Both miRNAs can then act as negative feedback regulators of the inflammatory response by targeting IRAK-1 or other modulators of the NF-κB or JAK/STAT signal transduction pathways for translational repression.