Fig. 1
From: Downregulation of the NLRP3 inflammasome by adiponectin rescues Duchenne muscular dystrophy
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-ĪŗB activation. Briefly, binding of LPS or IL-1Ī² 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 TNFĪ± 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-ĪŗB from its repressor IĪŗB, thereby permitting its translocation into the nucleus. This in turn upregulates transcription of pro-inflammatory factors such as TNFĪ± and inflammasome targets/components like pro-IL-1Ī²/-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-1Ī² 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, IĪŗB inhibitor of kappa B, IKK IĪŗB kinase, IL-1R interleukin-1 receptor, IRAK1/4 interleukin-1 receptor-associated kinase 1/4, LPS lipopolysaccharide, MyD88 myeloid differentiation primary response 88, NF-ĪŗB nuclear factor kappa B, PI3K phosphatidylinositol-4,5-bisphosphate 3-kinase, RIP1 receptor interacting protein 1, TAB1 transforming growth factor beta (TGF-Ī²) activated kinase 1-binding protein 1, TAK1 TGF-Ī² 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