Erlotinib protects against LPS-induced endotoxicity because TLR4 needs EGFR to signal.
Proc Natl Acad Sci U S A
; 112(31): 9680-5, 2015 Aug 04.
Article
en En
| MEDLINE
| ID: mdl-26195767
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Quinazolinas
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Transducción de Señal
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Lipopolisacáridos
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Sustancias Protectoras
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Receptor Toll-Like 4
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Receptores ErbB
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2015
Tipo del documento:
Article