Aryl hydrocarbon receptor deficiency enhanced airway inflammation and remodeling in a murine chronic asthma model

Yu Di Chang, Ching Hao Li, Chi Hao Tsai, Yu Wen Cheng, Jaw Jou Kang, Chen Chen Lee

研究成果: 雜誌貢獻文章同行評審

摘要

The aryl hydrocarbon receptor (AhR) is a ligand-dependent-activated transcriptional factor that regulates the metabolism of xenobiotic and endogenous compounds. Recent studies have shown that AhR is a novel master regulator of the mucosal immune system, including lungs and intestine. To elucidate the role of AhR in chronic severe asthma, AhR wild-type and knockout mice (AhR−/−) were sensitized and challenged with ovalbumin for 4 weeks. To uncover the underlying mechanisms, inflammatory cells profile and cytokines production were analyzed in bronchial lavage fluid (BALF) and lung tissue. Compared to wild-type mice, AhR−/− mice had exacerbated asthma symptoms, including airway inflammation, mucus production, airway hyperresponsiveness, and airway remodeling. BALF monocytes, neutrophils, eosinophils, and lymphocytes were all enhanced in OVA-immunized AhR−/− mice. In OVA-immunized AhR−/− mice, T helper (Th) 17 cell-specific cytokine IL-17A, as well as airway remodeling factors, including epithelial-mesenchymal transition (EMT) markers and vascular endothelial growth factor (VEGF), were all enhanced in lung tissue. Moreover, human cohort studies showed that AhR gene expression in bronchial epithelial cells decreases in severe asthma patients. Loss of AhR leads to worsening of allergic asthma symptoms, indicating its importance in maintaining normal lung function and mediating disease severity.
原文英語
頁(從 - 到)15300-15313
頁數14
期刊FASEB Journal
34
發行號11
DOIs
出版狀態接受/付印 - 2020

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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