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Cadmium induces mucin 8 expression via Toll‐like receptor 4–mediated extracellular signal related kinase 1/2 and p38 mitogen‐activated protein kinase in human airway epithelial cells
Author(s) -
Song SiYoun,
Bae Chang Hoon,
Choi Yoon Seok,
Kim YongDae
Publication year - 2016
Publication title -
international forum of allergy and rhinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.503
H-Index - 46
eISSN - 2042-6984
pISSN - 2042-6976
DOI - 10.1002/alr.21705
Subject(s) - mucin , mapk/erk pathway , small interfering rna , p38 mitogen activated protein kinases , kinase , signal transduction , protein kinase a , medicine , microbiology and biotechnology , biology , cancer research , transfection , biochemistry , pathology , gene
Background Inhalation of cadmium can lead to development of inflammatory airway diseases such as acute pulmonary edema and chronic obstructive pulmonary disease. In inflammatory airway diseases, expression of mucins is increased, which leads to increased morbidity and mortality of the affected patients. However, no study on the effect of cadmium on expression of mucin genes in airway epithelial cells has been reported. Therefore, this study was conducted in order to investigate the effect and the brief signaling pathway of cadmium on expression of mucin genes in human airway epithelial cells. Methods In mucin‐producing human NCI‐H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the effect and signaling pathway of cadmium on expression of mucin genes were investigated using reverse transcription–polymerase chain reaction (RT‐PCR), real‐time PCR, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering RNA (siRNA). Results Cadmium increased mucin 8 (MUC8) expression and Toll‐like receptor (TLR) 4 messenger RNA (mRNA) expression. Cadmium significantly activated phosphorylation of extracellular signal related kinase 1/2 (ERK1/2) mitogen‐activated protein kinase (MAPK) and p38 MAPK. ERK1/2 MAPK inhibitor, p38 MAPK inhibitor, TLR4 siRNA, ERK1/2 MAPK siRNA, and p38 MAPK siRNA significantly blocked cadmium‐induced MUC8 mRNA expression. TLR4 siRNA significantly blocked cadmium‐activated phosphorylation of ERK1/2 MAPK and p38 MAPK. Conclusion The results of this study suggest for the first time that cadmium induces MUC8 expression via TLR4‐mediated ERK1/2 and p38 MAPK signaling pathway in human airway epithelial cells.