Erlotinib protects against LPS-induced endotoxicity because TLR4 needs EGFR to signal
S De, H Zhou, D DeSantis… - Proceedings of the …, 2015 - National Acad Sciences
S De, H Zhou, D DeSantis, CM Croniger, X Li, GR Stark
Proceedings of the National Academy of Sciences, 2015•National Acad SciencesSeveral components of the canonical pathway of response to lipopolysaccharide (LPS) are
required for the EGF-dependent activation of NFκB. Conversely, the ability of Toll-like
Receptor 4 (TLR4) to activate NFκB in response to LPS is impaired by down regulating EGF
receptor (EGFR) expression or by using the EGFR inhibitor erlotinib. The LYN proto-
oncogene (LYN) is required for signaling in both directions. LYN binds to the EGFR upon
LPS stimulation, and erlotinib impairs this association. In mice, erlotinib blocks the LPS …
required for the EGF-dependent activation of NFκB. Conversely, the ability of Toll-like
Receptor 4 (TLR4) to activate NFκB in response to LPS is impaired by down regulating EGF
receptor (EGFR) expression or by using the EGFR inhibitor erlotinib. The LYN proto-
oncogene (LYN) is required for signaling in both directions. LYN binds to the EGFR upon
LPS stimulation, and erlotinib impairs this association. In mice, erlotinib blocks the LPS …
Several components of the canonical pathway of response to lipopolysaccharide (LPS) are required for the EGF-dependent activation of NFκB. Conversely, the ability of Toll-like Receptor 4 (TLR4) to activate NFκB in response to LPS is impaired by down regulating EGF receptor (EGFR) expression or by using the EGFR inhibitor erlotinib. The LYN proto-oncogene (LYN) is required for signaling in both directions. LYN binds to the EGFR upon LPS stimulation, and erlotinib impairs this association. In mice, erlotinib blocks the LPS-induced expression of tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) and ameliorates LPS-induced endotoxity, revealing that EGFR is essential for LPS-induced signaling in vivo.
National Acad Sciences