Figure 1

Inhibitory signals of the Toll-like receptor (TLR)4-induced MyD88-dependent signaling pathway. In addition to negative signals delivered by cytokines, cell surface receptors and numerous intracellular molecules down-regulate the TLR4-dependent signaling pathways following its activation by endotoxin (lipopolysaccharide (LPS)) (see text for further explanation). Small downwards and upwards arrows in squares indicate the down- or up-regulation, respectively, of the compound observed in endotoxin tolerant cells. Framed names of inhibitors indicate their demonstrated involvement in the endotoxin tolerance process. ABIN, A20 binding inhibitor of NF-κB activation; DUSP-1, dual specificity phosphatase 1; Erk, extracellular signal-related kinase; HO-1, heme oxygenase-1; IκB, inhibitor of κB; IRAK, IL-1 receptor associated kinase; MAPK, mitogen-activated protein kinase; MKP, MAPK phosphatase; MyD88, myeloid differentiation 88; NF-κB, nuclear factor-kappa B; pi3K, phosphatidylinositol 3-kinase; SHIP, SH1-containing inositol-5' phosphatase; SIGIRR, single immunoglobulin IL-1R-related molecule; SOCS, suppressor of cytokine signaling; STAT, signal transducer and activator of transcription; TAK1, TGFβ activating kinase 1; TGF, transforming growth factor; Tollip, Toll interacting protein; TRAF, TNF receptor associated factor.