Abstract
Background
The overexpression of TSLP and DNA methylation in asthma were both risk factors the relationship was not clear.
Objective
This study aimed to investigate the relationship between methylation status of TSLP promoter and mRNA/protein expression in asthmatic airway epithelial cells.
Methods
Human bronchial epithelial cells were cultured in vitro and divided into: Control group, treated with PBS, model group, sensitized with LPS (10 μg/mL) for 12 h (37 °C, 5% CO2). Other groups were cultured with the pCMV3 plasmid (M + NC/pCMV), pGPH1 plasmid (M + NC/pGPH), DNMT1/pCMV3 plasmid (M + DNMT1/pCMV), and DNMT1/pGPH1 plasmid (M + DNMT1/pGPH) for 48 h. The expression of DNA methyltransferase 1 and TSLP were measured using real-time PCR and western blotting.
Results
Compared with the control group, TSLP mRNA (1.00 ± 0.00 vs. 2.82 ± 0.81 vs. 1, P < 0.001) and protein (1.07 ± 0.04 vs. 1.46 ± 0.11, P < 0.01) were significantly greater, and the methylation of promoter was lower (92.75 ± 1.26 vs. 58.57 ± 3.34, P < 0.05) in the model group. Compared with the model group, TSLP mRNA (2.82 ± 0.81 vs. 1.17 ± 0.10, P < 0.001) decreased, but TSLP promoter methylation increased (58.57 ± 3.34 vs. 92.58 ± 7.30, P < 0.05) in M + DNMT1/pCMV. TSLP mRNA and protein were higher (2.82 ± 0.81 vs. 5.32 ± 0.21, P < 0.001; 1.46 ± 0.11 vs. 1.94 ± 0.11, respectively, P < 0.01), TSLP promoter methylation was lower (58.57 ± 3.34 vs. 33.57 ± 4.29, P < 0.05) in M + DNMT1/pGPH.
Conclusions
Overexpression of TSLP in asthmatic airway epithelial cells may be regulated by DNA demethylation.
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References
Brand S, Kesper DA, Teich R, Kilic-Niebergall E, Pinkenburg O, Bothur E, Lohoff M, Garn H, Pfefferle PI, Renz H (2012) DNA methylation of TH1/TH2 cytokine genes affects sensitization and progress of experimental asthma. J Allergy Clin Immunol 129:1602–1610. https://doi.org/10.1016/j.jaci.2011.12.963
Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, Adcock IM, Bateman ED, Bel EH, Bleecker ER, Boulet LP, Brightling C, Chanez P, Dahlen SE, Djukanovic R, Frey U, Gaga M, Gibson P, Hamid Q, Jajour NN, Mauad T, Sorkness RL, Teague WG (2014) International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir 43:343–373. https://doi.org/10.1183/09031936.00202013
Fan XY, van den Berg A, Snoek M, van der Flier LG, Smids B, Jansen HM, Liu RY, Lutter R (2009) Arginine deficiency augments inflammatory mediator production by airway epithelial cells in vitro. Respir Res 10:62. https://doi.org/10.1186/1465-9921-10-62
Gomez JL (2019) Epigenetics in asthma. Curr Allergy Asthma Rep 19:56. https://doi.org/10.1007/s11882-019-0886-y
Hu Y, Dong H, Zou M, Huang C, Luo L, Yu C, Chen J, Xie Z, Zhao H, Le Y, Zou F, Liu L, Cai S (2017) TSLP signaling blocking alleviates E-cadherin dysfunction of airway epithelium in a HDM induced asthma model. Cell Immunol 315:56–63. https://doi.org/10.1016/j.cellimm.2017.02.003
Le Souëf PN (2009) Gene–environmental interaction in the development of atopic asthma: new developments. Curr Opin Allergy Clin Immunol 9:123–127. https://doi.org/10.1097/ACI.0b013e3283292283
Lee PP, Fitzpatrick DR, Beard C, Jessup HK, Lehar S, Makar KW, Pérez-Melgosa M, Sweetser MT, Schlissel MS, Nguyen S, Cherry SR, Tsai JH, Tuckar SM, Weaver WM, Kelso A, Jaenisch R, Wilson CB (2001) A critical role for DNMT1 and DNA methylation in T cell development, function and survival. Immunity 15:763–774. https://doi.org/10.1016/s1074-7613(01)00227-8
Li YL, Li HJ, Ji F, Zhang X, Wang R, Hao JQ, Bi WX, Dong L (2010) Thymic stromal lymphopoietin promotes lung inflammation through activation of dendritic cells. J Asthma 47:117–123. https://doi.org/10.3109/02770900903483816
Li Y, Wang W, Lv Z, Li Y, Chen Y, Huang K, Corrigan CJ, Ying S (2018) Elevated expression of IL-33 and TSLP in the airways of human asthmatics in vivo: A potential biomarker of severe refractory disease. J Immunol 200:2253–2262. https://doi.org/10.4049/jimmunol.1701455
Luo Y, Zhou B, Zhao M, Tang J, Lu Q (2014) Promoter demethylation contributes to TSLP overexpression in skin lesions of patients with atopic dermatitis. Clin Exp Dermatol 39:48–53. https://doi.org/10.1111/ced.12206
Martino D, Prescott S (2011) Epigenetics and prenatal influences on asthma and allergic airways disease. Chest 139:640–647. https://doi.org/10.1378/chest.10-1800
Meng JF, Rosenwasser LJ (2010) Unraveling the genetic basis of asthma and allergic diseases. Allergy Asthma Immunol Res 2:215–227. https://doi.org/10.4168/aair.2010.2.4.215
Mitchell PD, O’Byrne PM (2017) Biologics and the lung: TSLP and other epithelial cell-derived cytokines in asthma. Pharmacol Ther 169:104–112. https://doi.org/10.1016/j.pharmthera.2016.06.009
Shenker N, Flanagan JM (2012) Intragenic DNA methylation: implications of this epigenetic mechanism for cancer research. Br J Cancer 106:248–253. https://doi.org/10.1038/bjc.2011.550
Song Y, Khoo SK, Lee KH, Mäkelä M, Haahtela T, LeSouëf P, Zhang GB (2017) Dual responses of CD14 methylation to distinct environments: a role in asthma and allergy. Eur Respir J 50:1701228. https://doi.org/10.1183/13993003.01228-2017
Soumelis V, Reche PA, Kanzler H, Yuan W, Edward G, Homey B, Gilliet M, Ho S, Antonenko S, Lauerma A, Smith K (2002) Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol 3:673–680. https://doi.org/10.1038/ni805
Verma M, Chattopadhyay BD, Paul BN (2013) Epigenetic regulation of DNMT1 gene in mouse model of asthma disease. Mol Biol Rep 40:2357–2368. https://doi.org/10.1007/s11033-012-2317-1
Wang IJ, Chen SL, Lu TP, Chuang EY, Chen PC (2013) Prenatal smoke exposure DNA methylation, and childhood atopic dermatitis. Clin Exp Allergy 43:535–543. https://doi.org/10.1111/cea.12108
Wang W, Li Y, Lv Z, Chen Y, Li Y, Huang K, Corrigan CJ, Ying S (2018) Bronchial allergen challenge of patients with atopic asthma triggers an alarmin (IL-33, TSLP, and IL-25) response in the airways epithelium and submucosa. J Immunol 201:2221–2231. https://doi.org/10.4049/jimmunol.1800709
Yang IV, Pedersen BS, Liu A, O’Connor GT, Teach SJ, Kattan M, Misiak RT, Gruchalla R, Steinbach SF, Szefler SJ, Gill MA, Calatroni A, David G, Hennessy CE, Davidson EJ, Zhang W, Gergen P, Togias A, Busse WW, Schwartz DA (2015) DNA methylation and childhood asthma in the inner city. J Allergy Clin Immunol 136:69–80. https://doi.org/10.1016/j.jaci.2015.01.025
Yang IV, Lozupone CA, Schwartz DA (2017) The environment, epigenome, and asthma. J Allergy Clin Immunol 140:14–23. https://doi.org/10.1016/j.jaci.2017.05.011
Zhong J, Sharma J, Raju R, Palapetta SM, Prasad TS, Huang TC, Yoda A, Tyner JW, van Bodegom D, Weinstock DM, Ziegler SF, Pandey A (2014) TSLP signaling pathway map: a platform for analysis of TSLP-mediated signaling. Database (Oxford). https://doi.org/10.1093/database/bau007
Acknowledgements
This work was supported by the Yunnan Applied Basic Research Projects-Joint Special Project (no. 2017FE468(-234)).
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Yan-Li Li, Xi-Qian Xing, Yi Xiao, Yan-Hong Liu, Yu-Shan Zhou, Min Zhuang and Chao-Qian Li declare that they have no conflict of interest.
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Li, YL., Xing, XQ., Xiao, Y. et al. Correlation between DNA methylation and Thymic Stromal Lymphopoietin expression in asthmatic airway epithelial cells. Genes Genom 42, 1399–1406 (2020). https://doi.org/10.1007/s13258-020-01000-z
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DOI: https://doi.org/10.1007/s13258-020-01000-z