Figure 2.

Post-transcriptional regulation of Il-6 expression by Regnase-1 in innate immune cells. (A) Schematic representation of mouse Regnase-1. The sequence of the DSGXXS motif is also shown. ZF, CCCH type zinc finger. (B) In unstimulated cells, Regnase-1 suppresses Il-6 production by degrading Il-6 mRNA through its 3′ UTR. Upon TLR stimulation, IKK complex phosphorylates Regnase-1 at Ser435 and Ser439, which results in the rapid degradation of Regnase-1 protein similar to IκBα. The transcribed Il-6 mRNA is thereby stabilized, which facilitates robust Il-6 production. At a later stage, de novo synthesis of Regnase-1 leads to the degradation of Il-6 mRNA and its own mRNA, promoting the resolution of inflammation.