國家衛生研究院 NHRI:Item 3990099045/13469

NHRI > National Institute of Environmental Health Sciences > Shau-Ku Huang > Periodical Articles > Item 3990099045/13469

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/13469

Title:	Benzo(a)pyrene enhanced dermatophagoides group 1 (Der f 1)-Induced TGF beta 1 signaling activation through the aryl hydrocarbon receptor-RhoA axis in asthma
Other Titles:	Benzo(a)pyrene enhanced dermatophagoides group 1 (Der f 1)-Induced TGF β 1 signaling activation through the aryl hydrocarbon receptor-RhoA axis in asthma
Authors:	Wang, ER;Tu, W;Do, DC;Xiao, XJ;Bhatti, SB;Yang, LT;Sun, XZ;Xu, DM;Yang, PC;Huang, SK;Gao, PS;Liu, ZG
Contributors:	National Institute of Environmental Health Sciences
Abstract:	We have previously demonstrated that benzo(a)pyrene (BaP) co-exposure with dermatophagoides group 1 allergen (Der f 1) can potentiate Der f 1-induced airway inflammation. The underlying mechanism, however, remains undetermined. Here we investigated the molecular mechanisms underlying the potentiation of BaP exposure on Der f 1-induced airway inflammation in asthma. We found that BaP co-exposure potentiated Der f 1-induced TGF beta 1 secretion and signaling activation in human bronchial epithelial cells (HBECs) and the airways of asthma mouse model. Moreover, BaP exposure alone or co-exposure with Der f 1-induced aryl hydrocarbon receptor (AhR) activity was determined by using an AhR-dioxin-responsive element reporter plasmid. The BaP and Der f 1 co-exposure-induced TGF beta 1 expression and signaling activation were attenuated by either AhR antagonist CH223191 or AhR knockdown in HBECs. Furthermore, AhR knockdown led to the reduction of BaP and Der f 1 co-exposure-induced active RhoA. Inhibition of RhoA signaling with fasudil, a RhoA/ROCK inhibitor, suppressed BaP and Der f 1 co-exposure-induced TGF beta 1 expression and signaling activation. This was further confirmed in HBECs expressing constitutively active RhoA (RhoA-L63) or dominant-negative RhoA (RhoA-N19). Luciferase reporter assays showed prominently increased promoter activities for the AhR binding sites in the promoter region of RhoA. Inhibition of RhoA suppressed BaP and Der f 1 co-exposure-induced airway hyper-responsiveness, Th2-associated airway inflammation, and TGF beta 1 signaling activation in asthma. Our studies reveal a previously unidentified functional axis of AhR-RhoA in regulating TGF beta 1 expression and signaling activation, representing a potential therapeutic target for allergic asthma.
Date:	2021-04-15
Relation:	Frontiers in Immunology. 2021 Apr 15;12:Article number 643260.
Link to:	http://dx.doi.org/10.3389/fimmu.2021.643260
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1664-3224&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000645118000001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85105023705
Appears in Collections:	[Shau-Ku Huang] Periodical Articles

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