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TLR3 inhibitor and tyrosine kinase inhibitor attenuate cigarette smoke/poly I:C-induced airway inflammation and remodeling by the EGFR/TLR3/MAPK signaling pathway.
Jiang, Jing-Jin; Chen, Si-Min; Li, Han-Yu; Xie, Qiang-Min; Yang, Yun-Mei.
Afiliação
  • Jiang JJ; Department of Geriatics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Disease, Hangzhou, 310003, China.
  • Chen SM; Department of Geriatics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Disease, Hangzhou, 310003, China.
  • Li HY; Department of Geriatics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Disease, Hangzhou, 310003, China.
  • Xie QM; Department of Geriatics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Disease, Hangzhou, 310003, China; Zhejiang Respiratory Drugs Research Laborator
  • Yang YM; Department of Geriatics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Disease, Hangzhou, 310003, China. Electronic address: 1194070@zju.edu.cn.
Eur J Pharmacol ; : 173654, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33068589
ABSTRACT
Tobacco smoke is the major risk factor for developing chronic obstructive pulmonary disease (COPD). Viral infection is a major cause of COPD exacerbation, which lacks effective drug treatments. In the present study, to mimic the pathogenesis of COPD, we employed a TLR3 ligand [Poly (IC), PIC] to mimic viral infection to determine whether it enhances the effects of cigarette smoke (CS)-induced airway inflammation and remodeling. Our results showed that PIC enhanced the effects of cigarette smoke extract (CSE)-induced inflammatory cytokine IL-1ß, TNF-α and IL-8 mRNA expression and remodeling factor E-cadherin, α-SMA and TGF-ß1 mRNA expression with TLR3 upregulation and EGFR phosphorylation in pulmonary epithelial NCI-H292 cells. These responses were inhibited by a TLR3/dsRNA complex inhibitor (TLR3i) or a tyrosine kinase inhibitor icotinib (Ico). Similarly, in the PIC-enhanced CS-induced airway inflammation and remodeling mouse model, treatment with TLR3i or Ico reduced the mRNA and protein expression of the inflammatory cytokines IL-1ß and TNF-α and keratinocyte chemoattractant (KC) and the remodeling factors α-SMA, TGF-ß1, MMP-9 and MUC5AC, while increasing E-cadherin mRNA and protein expression. Furthermore, we found that TLRi and Ico can attenuate the airway hyperreactivity induced by PIC, which is enhanced by CS. Finally, PIC enhanced the effects of CS on TLR3 upregulation and EGFR phosphorylation and significantly increased Erk1/2 and P38 phosphorylation, whereas TLR3i and Ico markedly suppressed TLR3 upregulation and EGFR, Erk1/2 and P38 phosphorylation in the model. Our findings suggest that TLR3/EGFR may be a potential target for the treatment of airway inflammation and remodeling in COPD.
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo prognóstico / Fatores de risco Idioma: Inglês Revista: Eur J Pharmacol Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: China

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo prognóstico / Fatores de risco Idioma: Inglês Revista: Eur J Pharmacol Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: China
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