title: 1,25-Dihydroxyvitamin D3 prevents toluene diisocyanate-induced airway epithelial barrier disruption.
abstract: The loss of airway epithelial integrity contributes significantly to asthma pathogenesis. Evidence suggests that vitamin D plays an important role in the prevention and treatment of asthma. However, its role in airway epithelial barrier function remains uncertain. We have previously demonstrated impaired epithelial junctions in a model of toluene diisocyanate (TDI)-induced asthma. In the present study, we hypothesized that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] may prevent TDI-induced epithelial barrier disruption. Male BALB/c mice were dermally sensitized and then challenged with TDI. The mice were then administered 1,25(OH)2D3 intraperitoneally prior to challenge with TDI. For in vitro experiments, 16HBE bronchial epithelial cells were cultured and stimulated with TDI-human serum albumin (HSA). The results revealed that the mice treated with 1,25(OH)2D3 displayed decreased airway hyperresponsiveness (AHR), suppressed neutrophil and eosinophil infiltration into the airways, as well as an increased E-cadherin and zonula occludens-1 (ZO-1) expression at the cell-cell contact sites. In vitro, exposure of the cells to TDI-HSA induced a rapid decline in transepithelial electrical resistance (TER) and an increase in cell permeability, followed by a decrease in occludin expression and the redistribution of E-cadherin, accompanied by a significant upregulation in the levels of phosphorylated extracellular signal-regulated kinase (ERK)1/2. These effects were all partly reversed by treatment with either 1,25(OH)2D3 or an ERK1/2 inhibitor. In conclusion, the findings of our study demonstrate that 1,25(OH)2D3 prevents TDI-induced epithelial barrier disruption, and that the ERK1/2 pathway may play a role in this process.
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Li
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Hangming
authors.initials: H
authors.lastname: Dong
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Haijin
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Song
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Haixiong
authors.initials: H
authors.lastname: Tang
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Yao
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Laiyu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Wancheng
authors.initials: W
authors.lastname: Tong
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Mengchen
authors.initials: M
authors.lastname: Zou
authors.affiliation: School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Shaoxi
authors.initials: S
authors.lastname: Cai
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D017097:Electric Impedance; D004804:Eosinophils / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects; D062793:Occludin / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology*; D019108:Tight Junctions / Q000473:pathology*; D014051:Toluene 2,4-Diisocyanate; D062826:Zonula Occludens-1 Protein / Q000096:biosynthesis
chemical_list: D015820:Cadherins; D062793:Occludin; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D014051:Toluene 2,4-Diisocyanate; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D048049:Extracellular Signal-Regulated MAP Kinases; D002117:Calcitriol