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. 2024 Jan 17;67(2):1225–1242. doi: 10.1021/acs.jmedchem.3c01714

Figure 1.

Figure 1

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.