Influence of o,p′-DDT on MUC5AC expression via regulation of NF-κB/AP-1 activation in human lung epithelial cells

ABSTRACT

o,p’-Dichlorodiphenyltrichloroethane (o,p’-DDT) is a representative endocrine disruptor, and exposure to o,p’-DDT may produce immune disorders and inflammation, leading to various diseases such as cancer. Chronic airway inflammation is characterized by excessive mucus secretion resulting in chronic obstructive pulmonary disease (COPD). Mucin 5AC  (MUC5AC), one of the mucus genes, plays an important role in mucus secretion and inflammation in the airways. The aim of this study was to examine the effects of o,p′-DDT on the regulation of MUC5AC expression in human lung epithelial A549 cell line. o,p′-DDT increased mRNA levels and the promoter activity of MUC5AC. Transient transfection with mutation promoter constructs of MUC5AC demonstrated that nuclear factor kappa-b (NF-κB) and activator protein 1(AP-1) response elements were essential for the consequences of o,p’-DDT on MUC5AC expression. In addition, o,p′-DDT induced phosphorylation of ERK, JNK, p38, and Akt, which are involved in the regulation of MUC5AC expression. It is noteworthy that inhibitors of NF-κB, AP-1, Akt, and MAPKs blocked enhanced o,p′-DDT-induced MUC5AC mRNA expression. Data indicate that o,p′-DDT increase in NF-κB, and AP-1 transcriptional activation-dependent MUC5AC expression is associated with stimulation of Akt and MAPK signaling pathways in A549 cells.

KEYWORDS:

• o
• p’-DDT
• MUC5AC
• NF-κB
• AP-1

Acknowledgments

This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2012R1A6A3A01019312) and Ministry of Science, ICT and Future Planning (NRF-2020R1A2C1007764).

Disclosure Statement

The authors declare that they have no conflict of interest.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.