Figure 2.

TLR4 signaling via MyD88-dependent and independent pathway to activate NFkB related target genes: Upon stimulation of myeloid differentiation primary response protein 88 (MyD88) dependent pathway involves the activation of MyD88 which recruits IL-1 receptor-associated kinase-4 (IRAK-4). IRAK-4 phosphorylates IRAK-1 and allows tumor necrosis factor receptor associated factor 6 (TRAF6) to associate with IRAK1. IRAK1/TRAF6 then activates TAK₁, TAB₁, and TAB₂. The TRAF6, TAK₁, TAB₁, and TAB₂ forms a larger complex with ubiquitin-conjugating enzyme E32 variant 1 isoform A (Ubc13) and Uev1A which activates TAK₁. Polyubiquitin chain is then removed by A20 and conserved cylindromatosis (CYLD). Activated TAK₁ phosphorylates the IKK complex (IKKα. IKKβ and IKKγ) ultimately resulting in the translocation of nuclear factor-κB (NF-κB) into the nucleus, resulting in the transcription of proinflammatory cytokines. MyD88 independent pathway involves TIR-domain-containing adapter-inducing interferon-β (TRIF) leading to the activation of TNF receptor associated factor 3 (TRAF3) and the translocation of interferon regulatory factor 3 (IRF3) to the nucleus leading to IFNB gene transcription. Image made using BioRender.