Table 1 The target and mechanism of A20 regulating arthritis
Target | Pro-inflammation approach | Effect of A20 | Consequence |
|---|---|---|---|
NF-κB | Trigger the formation of numerous pro-inflammatory cytokines like IFN-γ, TNF-α, IL-1β, IL-6 | Restrict its activation | Reduced pro-inflammation cytokines |
Casp1 | Cell pyroptosis | Lower activation of Casp1 and inhibit pyroptosis dependent on Casp1 | Cell survival and secretion of cytokines is blocked |
NLRP3 activation, IL-1 and IL-18 secretion | Downregulate the transcription of NLRP3, ASC, procaspase1, proIL-1, and IL-18 | Inhibited NLRP3 assembly and activation | |
RIPK1 | Activation of NF-κB | Remove K63-linked ubiquitin chains from RIPK1 and add K48-linked ubiquitin on RIPK1 | Degradation of RIPK1 |
Substrate of Casp8 | |||
MAPKs | Secretion of IL-17A | Deubiquitination of TRAF6 and prevent the prolonged phosphorylation of JNK | Blocked IL-17 production |
Unphosphorylated RIPK3 | Macrophages necroptosis | Reduce phosphorylation of RIPK3 | Macrophages survived |
TNFR1 signal complexes | Macrophages necroptosis | Protect these complexes from being degraded through ZnF7 domain | Macrophages survived |