Fig. 1.

Inflammation/immune signalling pathways repressed by miR-711 in muscle. The target genes of miR-711 are indicated in bold and outlined in black. They are involved in inflammatory/immune signalling pathways that split into two branches. The first one, depicted in grey, has been recently described [11] and results in NF-κB activation. Briefly, binding of LPS or IL-1β to their respective receptor TLR4 or IL-1R triggers the assembly of a complex (composed of MyD88 and TOLLIP), while activation of TNFR signalling by TNFα triggers the assembly of another complex including TRADD. These intracellular scaffolds stimulate the IKK complex through activation of TAB1 or PI3K. Next, the IKK complex releases NF-κB from its repressor IκB, thereby permitting its translocation into the nucleus. This in turn upregulates transcription of pro-inflammatory factors such as TNFα and inflammasome targets/components like pro-IL-1β/-18 and NLRP3 (i.e. priming of NLRP3). The second branch in fuchsia leads through FADD and caspase-8 activation to NLRP3 activation. FADD can be recruited by the TRADD or MyD88 complex. Inflammasome activation involves assembly of NLRP3 with ASC and pro-caspase-1. This complex triggers pro-caspase-1 self-cleavage into active caspase-1, which then cleaves pro-IL-1β and pro-IL-18 into their biologically active cytokines. Abbreviations: AKT protein kinase B, ASC apoptosis-associated speck-like protein, FADD Fas-associated protein with death domain, IκB inhibitor of kappa B, IKK IκB kinase, IL-1R interleukin-1 receptor, IRAK1/4 interleukin-1 receptor-associated kinase 1/4, LPS lipopolysaccharide, MyD88 myeloid differentiation primary response 88, NF-κB nuclear factor kappa B, PI3K phosphatidylinositol-4,5-bisphosphate 3-kinase, RIP1 receptor interacting protein 1, TAB1 transforming growth factor beta (TGF-β) activated kinase 1-binding protein 1, TAK1 TGF-β activated kinase 1, TIRAP Toll-interleukin 1 receptor domain-containing adapter protein, TLR4 Toll-like receptor 4, TNFR tumour necrosis factor receptor, TOLLIP Toll interacting protein, TRADD TNFR type 1-associated death domain protein, TRAF2/6 TNFR associated factor 2/6