Danger Signals in the Initiation of the Inflammatory Response after Myocardial Infarction

Figure 1

DAMP signaling through different PRRs. TLR activation by DAMPS triggers adaptor proteins MyD88, TRIF, TIRAP, or TRAM to activate various transcriptions factors. The subsequent translocation of NF-κB and MAPK leads to the production of several proinflammatory cytokines. TRIF-dependent activation of transcription factors IRF3 and IRF7 results in the induction of type I interferon. Additionally, the TLR- NF-κB pathway can induce the transcription of pro-IL-1β, pro-IL-18, and other components of the inflammasome pathway. Inflammasome activation is considered to depend on two distinct signals. The first signal via TLR and this might be the rate limiting step for inflammasome assembly and activity; the second signal via NLR which is responsible for inflammasome assembly, caspase-1 activation, and secretion of IL-1β and IL-18. Activation of NOD receptors results in activation of the NF-κB pathway.