1. Methylation status of ORMDL3 regulates cytokine production and p-ERK/MMP9 pathway expression.
- Author
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Wu XL, Li R, Zhang HW, Jin R, Wang JY, Juan CX, Lu K, Shu J, Wang LL, Wang Y, Zhuang LL, and Zhou GP
- Subjects
- Adolescent, Asthma metabolism, Asthma pathology, Base Sequence, Case-Control Studies, Cell Line, Transformed, Child, CpG Islands, Decitabine pharmacology, Epithelial Cells drug effects, Epithelial Cells metabolism, Epithelial Cells pathology, Female, Humans, Interleukin-6 genetics, Interleukin-6 metabolism, Interleukin-8 genetics, Interleukin-8 metabolism, Male, Matrix Metalloproteinase 9 metabolism, Membrane Proteins metabolism, Methylation, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Promoter Regions, Genetic, Respiratory Mucosa metabolism, Respiratory Mucosa pathology, Signal Transduction, Asthma genetics, Epigenesis, Genetic, Matrix Metalloproteinase 9 genetics, Membrane Proteins genetics, Mitogen-Activated Protein Kinase 1 genetics, Mitogen-Activated Protein Kinase 3 genetics
- Abstract
Orosomucoid like-3 (ORMDL3) has been identified to be associated with the development of asthma according to previous studies. However, the definite role of ORMDL3 in the pathogenesis of asthma remains unclear. In this study, we found ORMDL3 was highly expressed in PBMC specimens from childhood asthma patients. Cytokines production and p-ERK/MMP-9 pathway expression was also increased in childhood asthma patients compared with controls. In addition, ORMDL3 overexpression induced IL-6 and IL-8 release and activated p-ERK/MMP-9 pathway in vitro. Increased ORMDL3 expression was observed after treated with 5-Aza-CdR. 5-Aza-CdR decreased the percentage of the CpG island in the ORMDL3 promoter region and increased its promoter activity. In addition, 5-Aza-CdR significantly increased IL-6 and IL-8 levels in NHBE cells while there was no obvious alteration after knocking down ORMDL3. Knockdown of ORMDL3 also significantly decreased the expression of p-ERK/MMP-9 pathway in the presence or absence of 5-Aza-CdR. In conclusion, our study provided novel evidence for the association between ORMDL3 and asthma-associated cytokines. Moreover, DNA methylation plays an important role in ORMDL3-mediated increased IL-6 and IL-8 levels and p-ERK/MMP-9 pathway expression., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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