House dust mites stimulate thymic stromal lymphopoietin production in human bronchial epithelial cells and promote airway remodeling through activation of PAR2 and ERK signaling pathway.

Autor: Hsieh YA; Division of Chest Medicine, Department of Internal Medicine, Asia University Hospital, No. 222, Fuxin Road, Wufeng District, 413505, Taichung City, Taiwan, ROC., Hsiao YH; Department of Chest Medicine, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Road., Beitou District, 11217, Taipei City, Taiwan, ROC.; School of Medicine, National Yang Ming Chiao Tung University, Yangming Campus, No. 155, Sec. 2, Linong Street, Beitou District, Taipei City, Taiwan, ROC., Ko HK; Department of Chest Medicine, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Road., Beitou District, 11217, Taipei City, Taiwan, ROC.; School of Medicine, National Yang Ming Chiao Tung University, Yangming Campus, No. 155, Sec. 2, Linong Street, Beitou District, Taipei City, Taiwan, ROC., Shen YL; Division of Chest Medicine, Department of Internal Medicine, Asia University Hospital, No. 222, Fuxin Road, Wufeng District, 413505, Taichung City, Taiwan, ROC., Huang CW; Division of Chest Medicine, Department of Internal Medicine, Asia University Hospital, No. 222, Fuxin Road, Wufeng District, 413505, Taichung City, Taiwan, ROC.; Department of Medical Laboratory Science and Biotechnology, Asia University, No. 500, Lioufeng Road, Wufeng District, 413305, Taichung City, Taiwan, ROC., Perng DW; Department of Chest Medicine, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Road., Beitou District, 11217, Taipei City, Taiwan, ROC. dwperng@vghtpe.gov.tw.; School of Medicine, National Yang Ming Chiao Tung University, Yangming Campus, No. 155, Sec. 2, Linong Street, Beitou District, Taipei City, Taiwan, ROC. dwperng@vghtpe.gov.tw.; Division of General Chest Medicine, Department of Chest Medicine, Taipei Veterans General Hospital, School of Medicine, Yangming Campus, National Yang Ming Chiao Tung University, No.201, Sec. 2, Shipai Rd., Beitou District, 11217, Taipei, Taiwan, ROC. dwperng@vghtpe.gov.tw., Su KC; Department of Chest Medicine, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Road., Beitou District, 11217, Taipei City, Taiwan, ROC. kcsu@vghtpe.gov.tw.; School of Medicine, National Yang Ming Chiao Tung University, Yangming Campus, No. 155, Sec. 2, Linong Street, Beitou District, Taipei City, Taiwan, ROC. kcsu@vghtpe.gov.tw.; Division of Clinical Respirology Physiology, Department of Chest Medicine, Taipei Veterans General Hospital, School of Medicine, Yangming Campus, National Yang Ming Chiao Tung University, No.201, Sec. 2, Shipai Rd., Beitou District, 11217, Taipei, Taiwan, ROC. kcsu@vghtpe.gov.tw.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Nov 19; Vol. 14 (1), pp. 28649. Date of Electronic Publication: 2024 Nov 19.
DOI: 10.1038/s41598-024-79226-0
Abstrakt: House dust mites (HDM) are common aeroallergens linked to airway inflammation and remodeling in asthma. Protease-activated receptor 2 (PAR2) and thymic stromal lymphopoietin (TSLP) may mediate these immune responses. However, how the epithelium influences fibroblasts toward airway remodeling remains unclear. We hypothesize that HDM stimulates human bronchial epithelial cells (HBECs) to produce TSLP via PAR2 activation, driving fibroblasts toward remodeling processes. HBECs were treated with HDM, with or without the PAR2 antagonist FSLLRY-NH2 (FSL), and TSLP expression was measured by qPCR and ELISA. Phosphorylation of MAPKs was assessed by western blotting. Human lung fibroblasts (HLFs) were exposed to recombinant TSLP or conditioned medium (CM) from HDM-stimulated HBECs, with or without anti-TSLP antibodies. Fibroblast proliferation and collagen production were assessed as remodeling markers. HDM increased ERK phosphorylation (not p38 or JNK) and TSLP expression at mRNA and protein levels. FSL preincubation significantly reduced ERK phosphorylation and TSLP production: HDM-stimulated CM induced fibroblast proliferation and collagen production, effects suppressed by anti-TSLP or FSL. Direct treatment with recombinant TSLP also promoted fibroblast proliferation and collagen synthesis. These findings suggest that HDM promotes HBEC-to-HLF paracrine interactions via PAR2-ERK-TSLP axis, participating in airway remodeling. PAR2 antagonists may represent potential therapeutic targets for HDM-induced remodeling processes.
Competing Interests: Declarations Conflict of interest All authors declare that they have no conflict of interest. Ethics approval This study was approved by the Institutional Review Board of Taipei Veterans General Hospital (ID 2019-08-004B).
(© 2024. The Author(s).)
Databáze: MEDLINE
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