1,25-Dihydroxyvitamin D3 prevents toluene diisocyanate-induced airway epithelial barrier disruption

Li,Wenjia; Dong,Hangming; Zhao,Haijin; Song,Jiafu; Tang,Haixiong; Yao,Lihong; Liu,Laiyu; Tong,Wancheng; Zou,Mengchen; Zou,Fei; Cai,Shaoxi

doi:10.3892/ijmm.2015.2214

1,25-Dihydroxyvitamin D3 prevents toluene diisocyanate-induced airway epithelial barrier disruption

Authors:
- Wenjia Li
- Hangming Dong
- Haijin Zhao
- Jiafu Song
- Haixiong Tang
- Lihong Yao
- Laiyu Liu
- Wancheng Tong
- Mengchen Zou
- Fei Zou
- Shaoxi Cai
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Affiliations: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China, Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, P.R. China
Published online on: May 19, 2015 https://doi.org/10.3892/ijmm.2015.2214
Pages: 263-270

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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.

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1	Holgate ST: The airway epithelium is central to the pathogenesis of asthma. Allergol Int. 57:1–10. 2008. View Article : Google Scholar : PubMed/NCBI
2	Nawijn MC, Hackett TL, Postma DS, van Oosterhout AJ and Heijink IH: E-cadherin: Gatekeeper of airway mucosa and allergic sensitization. Trends Immunol. 32:248–255. 2011. View Article : Google Scholar : PubMed/NCBI
3	de Boer WI, Sharma HS, Baelemans SM, Hoogsteden HC, Lambrecht BN and Braunstahl GJ: Altered expression of epithelial junctional proteins in atopic asthma: Possible role in inflammation. Can J Physiol Pharmacol. 86:105–112. 2008. View Article : Google Scholar : PubMed/NCBI
4	Xiao C, Puddicombe SM, Field S, et al: Defective epithelial barrier function in asthma. J Allergy Clin Immunol. 128:549–556. 2011. View Article : Google Scholar : PubMed/NCBI
5	Post S, Nawijn MC, Hackett TL, Baranowska M, Gras R, van Oosterhout AJ and Heijink IH: The composition of house dust mite is critical for mucosal barrier dysfunction and allergic sensitisation. Thorax. 67:488–495. 2012. View Article : Google Scholar
6	Paul G, Brehm JM, Alcorn JF, Holguín F, Aujla SJ and Celedón JC: Vitamin D and asthma. Am J Respir Crit Care Med. 185:124–132. 2012. View Article : Google Scholar :
7	Zhao H, Peng H, Cai SX, Li W, Zou F and Tong W: Toluene diisocyanate enhances human bronchial epithelial cells’ permeability partly through the vascular endothelial growth factor pathway. Clin Exp Allergy. 39:1532–1539. 2009. View Article : Google Scholar : PubMed/NCBI
8	Song J, Zhao H, Dong H, Zhang D, Zou M, Tang H, Liu L, Liang Z, Lv Y, Zou F and Cai S: Mechanism of E-cadherin redistribution in bronchial airway epithelial cells in a TDI-induced asthma model. Toxicol Lett. 220:8–14. 2013. View Article : Google Scholar : PubMed/NCBI
9	Son M, Lee M, Kim YT, Youn JK and Park H: Heterogeneity of IgE response to TDI-HSA conjugates by ELISA in toluene diisocyanate (TDI)-induced occupational asthma (OA) patients. J Korean Med Sci. 13:147–152. 1998. View Article : Google Scholar : PubMed/NCBI
10	Wan H, Winton HL, Soeller C, Stewart GA, Thompson PJ, Gruenert DC, Cannell MB, Garrod DR and Robinson C: Tight junction properties of the immortalized human bronchial epithelial cell lines Calu-3 and 16HBE14o-. Eur Respir J. 15:1058–1068. 2000. View Article : Google Scholar : PubMed/NCBI
11	Zhao H, Zhang H, Wu H, Li H, Liu L, Guo J, Li C, Shih DQ and Zhang X: Protective role of 1,25(OH)2 vitamin D₃ in the mucosal injury and epithelial barrier disruption in DSS-induced acute colitis in mice. BMC Gastroenterol. 12:572012. View Article : Google Scholar
12	Petecchia L, Sabatini F, Varesio L, Camoirano A, Usai C, Pezzolo A and Rossi GA: Bronchial airway epithelial cell damage following exposure to cigarette smoke includes disassembly of tight junction components mediated by the extracellular signal-regulated kinase 1/2 pathway. Chest. 135:1502–1512. 2009. View Article : Google Scholar : PubMed/NCBI
13	Sekiyama A, Gon Y, Terakado M, Takeshita I, Kozu Y, Maruoka S, Matsumoto K and Hashimoto S: Glucocorticoids enhance airway epithelial barrier integrity. Int Immunopharmacol. 12:350–357. 2012. View Article : Google Scholar : PubMed/NCBI
14	Tarlo SM and Lemiere C: Occupational asthma. N Engl J Med. 370:640–649. 2014. View Article : Google Scholar : PubMed/NCBI
15	Ban M, Morel G, Langonné I, Huguet N, Pépin E and Binet S: TDI can induce respiratory allergy with Th2-dominated response in mice. Toxicology. 218:39–47. 2006. View Article : Google Scholar
16	De Vooght V, Smulders S, Haenen S, Belmans J, Opdenakker G, Verbeken E, Nemery B, Hoet PH and Vanoirbeek JA: Neutrophil and eosinophil granulocytes as key players in a mouse model of chemical-induced asthma. Toxicol Sci. 131:406–418. 2013. View Article : Google Scholar
17	Piirilä PL, Meuronen A, Majuri ML, Luukkonen R, Mäntylä T, Wolff HJ, Nordman H, Alenius H and Laitinen A: Inflammation and functional outcome in diisocyanate-induced asthma after cessation of exposure. Allergy. 63:583–591. 2008. View Article : Google Scholar : PubMed/NCBI
18	Talini D, Novelli F, Bacci E, Costa F, Dente FL, Di Franco A, Malagrinò L, Vagaggini B and Paggiaro P: Mild improvement in symptoms and pulmonary function in a long-term follow-up of patients with toluene diisocyanate-induced asthma. Int Arch Allergy Immunol. 161:189–194. 2013. View Article : Google Scholar : PubMed/NCBI
19	Gorman S, Weeden CE, Tan DH, Scott NM, Hart J, Foong RE, Mok D, Stephens N, Zosky G and Hart PH: Reversible control by vitamin D of granulocytes and bacteria in the lungs of mice: An ovalbumin-induced model of allergic airway disease. PLoS One. 8:e678232013. View Article : Google Scholar : PubMed/NCBI
20	Agrawal T, Gupta GK and Agrawal DK: Vitamin D supplementation reduces airway hyperresponsiveness and allergic airway inflammation in a murine model. Clin Exp Allergy. 43:672–683. 2013.PubMed/NCBI
21	Samrah S, Khatib I, Omari M, Khassawneh B, Momany S, Daoud A, Malkawi M and Khader Y: Vitamin D deficiency and level of asthma control in women from North of Jordan: A case-control study. J Asthma. 51:832–838. 2014. View Article : Google Scholar : PubMed/NCBI
22	Griffin MD, Xing N and Kumar R: Vitamin D and its analogs as regulators of immune activation and antigen presentation. Annu Rev Nutr. 23:117–145. 2003. View Article : Google Scholar : PubMed/NCBI
23	Herr C, Shaykhiev R and Bals R: The role of cathelicidin and defensins in pulmonary inflammatory diseases. Expert Opin Biol Ther. 7:1449–1461. 2007. View Article : Google Scholar : PubMed/NCBI
24	Hawrylowicz CM and O’Garra A: Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Nat Rev Immunol. 5:271–283. 2005. View Article : Google Scholar : PubMed/NCBI
25	Urry Z, Xystrakis E, Richards DF, McDonald J, Sattar Z, Cousins DJ, Corrigan CJ, Hickman E, Brown Z and Hawrylowicz CM: Ligation of TLR9 induced on human IL-10-secreting Tregs by 1alpha,25-dihydroxyvitamin D₃ abrogates regulatory function. J Clin Invest. 119:387–398. 2009.PubMed/NCBI
26	Barrat FJ, Cua DJ, Boonstra A, Richards DF, Crain C, Savelkoul HF, de Waal-Malefyt R, Coffman RL, Hawrylowicz CM and O’Garra A: In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J Exp Med. 195:603–616. 2002. View Article : Google Scholar : PubMed/NCBI
27	Xystrakis E, Kusumakar S, Boswell S, et al: Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. J Clin Invest. 116:146–155. 2006. View Article : Google Scholar
28	Kreindler JL, Steele C, Nguyen N, et al: Vitamin D₃ attenuates Th2 responses to Aspergillus fumigatus mounted by CD4⁺ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis. J Clin Invest. 120:3242–3254. 2010. View Article : Google Scholar : PubMed/NCBI
29	Mahon BD, Wittke A, Weaver V and Cantorna MT: The targets of vitamin D depend on the differentiation and activation status of CD4 positive T cells. J Cell Biochem. 89:922–932. 2003. View Article : Google Scholar : PubMed/NCBI
30	Georas SN and Rezaee F: Epithelial barrier function: At the front line of asthma immunology and allergic airway inflammation. J Allergy Clin Immunol. 134:509–520. 2014. View Article : Google Scholar : PubMed/NCBI
31	Yin Z, Pintea V, Lin Y, Hammock BD and Watsky MA: Vitamin D enhances corneal epithelial barrier function. Invest Ophthalmol Vis Sci. 52:7359–7364. 2011. View Article : Google Scholar : PubMed/NCBI