Correlation between DNA methylation and Thymic Stromal Lymphopoietin expression in asthmatic airway epithelial cells

다국어 초록 (Multilingual 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.

참고문헌 (Reference)

1 Lanny J Rosenwasser, "Unraveling the Genetic Basis of Asthma and Allergic Diseases" 대한천식알레르기학회 2 (2): 215-227, 2010

2 Li YL, "Thymic stromal lymphopoietin promotes lung inflammation through activation of dendritic cells" 47 : 117-123, 2010

3 Yang IV, "The environment, epigenome, and asthma" 140 : 14-23, 2017

4 Zhong J, "TSLP signaling pathway map: a platform for analysis of TSLP-mediated signaling" 2014

5 Hu Y, "TSLP signaling blocking alleviates E-cadherin dysfunction of airway epithelium in a HDM induced asthma model" 315 : 56-63, 2017

6 Luo Y, "Promoter demethylation contributes to TSLP overexpression in skin lesions of patients with atopic dermatitis" 39 : 48-53, 2014

7 Wang IJ, "Prenatal smoke exposure DNA methylation, and childhood atopic dermatitis" 43 : 535-543, 2013

8 Shenker N, "Intragenic DNA methylation : implications of this epigenetic mechanism for cancer research" 106 : 248-253, 2012

9 Chung KF, "International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma" 43 : 343-373, 2014

10 Soumelis V, "Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP" 3 : 673-680, 2002

11 Le Souëf PN, "Gene–environmental interaction in the development of atopic asthma : new developments" 9 : 123-127, 2009

12 Gomez JL, "Epigenetics in asthma" 19 : 56-, 2019

13 Martino D, "Epigenetics and prenatal influences on asthma and allergic airways disease" 139 : 640-647, 2011

14 Verma M, "Epigenetic regulation of DNMT1 gene in mouse model of asthma disease" 40 : 2357-2368, 2013

15 Li Y, "Elevated expression of IL-33 and TSLP in the airways of human asthmatics in vivo : A potential biomarker of severe refractory disease" 200 : 2253-2262, 2018

16 Song Y, "Dual responses of CD14 methylation to distinct environments : a role in asthma and allergy" 50 : 1701228-, 2017

17 Brand S, "DNA methylation of TH1/TH2 cytokine genes affects sensitization and progress of experimental asthma" 129 : 1602-1610, 2012

18 Yang IV, "DNA methylation and childhood asthma in the inner city" 136 : 69-80, 2015

19 Wang W, "Bronchial allergen challenge of patients with atopic asthma triggers an alarmin(IL-33, TSLP, and IL-25)response in the airways epithelium and submucosa" 201 : 2221-2231, 2018

20 Mitchell PD, "Biologics and the lung : TSLP and other epithelial cell-derived cytokines in asthma" 169 : 104-112, 2017

21 Fan XY, "Arginine deficiency augments inflammatory mediator production by airway epithelial cells in vitro" 10 : 62-, 2009

22 Lee PP, "A critical role for DNMT1 and DNA methylation in T cell development, function and survival" 15 : 763-774, 2001