IRAK4
plays a central role in TLR/IL-1R signaling pathways. Recognition
of different TLR ligands, such as oxidized low-density lipoproteins
(oLDL), high mobility group box 1 (HMGB1) protein, heat shock protein
(HSP), S100 family member proteins, and single stranded ribonucleic
acid (ssRNA) by TLRs or recognition of the IL-1R ligands initiates
the recruitment of myeloid differentiation primary response protein
88 (MyD88) to the respective receptor and subsequent activation of
IRAK4. This facilitates the activation of further downstream processes
like the NF-κB pathway or the MAPK pathway via IRAK1, IRAK2,
and tumor necrosis factor receptor associated factor 6 (TRAF6). The
activation of these pathways results in the expression of pro-inflammatory
cytokines, the enhanced stability of mRNA, cell differentiation and
expansion, driving inflammation and inflammatory pain. IKK, inhibitor
of NF-κB kinase; IRAK, interleukin-1 receptor-associated kinase;
MKK, MAPK kinase.