Korean J Otorhinolaryngol-Head Neck Surg.  2017 May;60(5):222-231. 10.3342/kjorl-hns.2016.17594.

Asian Sand Dust Up-Regulates MUC4 Expression in Human Upper Airway Epithelial Cells

• Park CH
• Song YS
• Bae CH
• Choi YS
• Song SY
• Shin KC
• Jin HJ
• Kim YD

• KMID: 2379917
• DOI: http://doi.org/10.3342/kjorl-hns.2016.17594

Abstract

BACKGROUND AND OBJECTIVES
Asian sand dust (ASD) is a meteorological phenomenon that occurs in spring time in Korea. ASD is composed of various organic and inorganic materials, which induce airway inflammation. MUC4 is an important membrane-bound mucin gene in the human airway, and its expression is increased in pathologic proliferative lesions such as nasal polyps. However, the effect of ASD on MUC4 in human airway epithelial cells is unclear. Therefore, this study aimed to investigate the effect and signaling pathway of ASD on MUC4 expressions in human airway epithelial cells. METERIALS AND METHOD: The effect and signaling pathway of ASD on MUC4 expressions were investigated in NCI-H292 cells and in the primary cultures of human nasal epithelial cells using reverse transcription-polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering ribonucleic acid (siRNA).
RESULTS
ASD induced MUC4 expression and the activated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). An ERK1/2 MAPK inhibitor and a p38 MAPK inhibitor inhibited the ASD-induced MUC4 expression. In addition, the knockdowns of ERK1, ERK2 and p38 MAPK by the respective siRNA blocked the ASD-induced MUC4 mRNA expression. ASD induced toll-like receptor 4 (TLR4) mRNA expression. The knockdown of TLR4 by TLR4 siRNA blocked the phosphorylation of ERK1/2 and p38 MAPK, and the ASD-induced MUC4 mRNA expression.
CONCLUSION
These results show that ASD induces MUC4 expressions via TLR4-dependent ERK1/2 and p38 MAPK signaling pathway in human airway epithelial cells.

Keyword

Airway epithelial cells; Asian sand dust; Mitogen-activated protein kinase; MUC4; Toll-like receptor 4

MeSH Terms

Asian Continental Ancestry Group*
Dust*
Epithelial Cells*
Humans
Humans*
Immunoenzyme Techniques
Inflammation
Korea
Methods
Mucins
Nasal Polyps
p38 Mitogen-Activated Protein Kinases
Phosphorylation
Phosphotransferases
Protein Kinases
Real-Time Polymerase Chain Reaction
RNA
RNA, Messenger
RNA, Small Interfering
Toll-Like Receptor 4
Dust
Mucins
Phosphotransferases
Protein Kinases
RNA
RNA, Messenger
RNA, Small Interfering
Toll-Like Receptor 4
p38 Mitogen-Activated Protein Kinases