Erlotinib protects against LPS-induced Endotoxicity because TLR4 needs EGFR to signal

• DOI: 10.1073/pnas.1511794112
• Publication Date: 2015-07-21T00:23:40Z
• Authors: Sarmishtha De; Hao Zhou; David DeSantis; Colleen M. Croniger; Xiaoxia Li; George R. Stark
• Keywords: Lipopolysaccharides; 0301 basic medicine; Epidermal Growth Factor; Tumor Necrosis Factor-alpha; NF-kappa B; MAP Kinase Kinase Kinases; Protective Agents; Proto-Oncogene Mas; Cell Line; 3. Good health; ErbB Receptors; Toll-Like Receptor 4; Erlotinib Hydrochloride; Mice; 03 medical and health sciences; Myeloid Differentiation Factor 88; Quinazolines; Animals; Cytokines; Humans; Gene Silencing; Phosphorylation; Signal Transduction

Several components of the canonical pathway response to lipopolysaccharide (LPS) are required for EGF-dependent activation NFκB. Conversely, ability Toll-like Receptor 4 (TLR4) activate NFκB in LPS is impaired by down regulating EGF receptor (EGFR) expression or using EGFR inhibitor erlotinib. The LYN proto-oncogene (LYN) signaling both directions. binds upon stimulation, and erlotinib impairs this association. In mice, blocks LPS-induced tumor necrosis factor α (TNFα) interleukin-6 (IL-6) ameliorates endotoxity, revealing that essential vivo.