Fig. 2
From: HMGB1 and Toll-like receptors: potential therapeutic targets in autoimmune diseases
HMGB1 and TLRs signaling pathway. HMGB1 can combined with cell surface TLRs (TLR1, TLR2, TLR4, TLR5, TLR6), while the nucleic acid of HMGB1 can cross the cell membrane and bind to the endosomal TLRs (TLR3, TLR7, TLR8, TLR9). TLRs recruit TIR domain-containing adaptor proteins like MyD88 and TRIF, which activate NF-κB signaling and IRFs. This initiates the expression of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, IFN-γ or the type I interferons IFN-α and IFN-β. The figure distinguishes by color the adaptor proteins MyD88 and TRIF that bind to different TLRs. TRIF: TIR domain-containing adaptor protein inducing IFNβ, MyD88: molecule myeloid differentiation primary response differentiation gene 88, NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells, IRF: Interferon Regulatory Factor, IFN: Interferon, TNF-α: tumor necrosis factor-alpha, IL: Interleukin