Figure 1

Schematic overview of Toll-like receptor (TLR)4 signaling pathway. LPS interacts with circulating LPS-binding protein (LBP) and binds to TLR4 on the cell membrane with two co-receptors (CD14 and myeloid differentiation protein (MD)2), activating myeloid differentiation factor (MyD)88-dependent and (MyD)88-independent TLR4 signaling via different adaptor proteins. The MyD88-dependent pathway signals through activation of iκB kinase (IKK) and mitogen activated protein kinase (MAPK) pathways, which in turn leads to activation of transcription factors nuclear factor (NF)-κB and activator protein (AP)-1, respectively, and controls the expression of pro-inflammatory cytokines and other immune related genes. In addition, phosphatidylinositol 3-kinase (PI3K) and AKT are also important factors downstream of MyD88 that mediate NF-κB activation. The MyD88-independent pathway is mediated by the TIR domain-containing adaptor inducing interferon-β (TRIF), which activates interferon regulatory (IRF)3 and induces the expression of interferon (IFN)-β and IFN-responsive genes