사람 상부 호흡기 상피세포에서 황사에 의한 MUC4 점소의 과발현
Asian Sand Dust Up-Regulates MUC4 Expression in Human Upper Airway Epithelial Cells
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초록
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. Korean J Otorhinolaryngol-Head Neck Surg 2017;60(5):222-31
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. Korean J Otorhinolaryngol-Head Neck Surg 2017;60(5):222-31
참고문헌 (16)
- Ali MS, "Upper airway mucin gene expression: a review", Laryngoscope, 117(5), pp.932~938 (2007)
- Williams OW, "Airway mucus: from production to secretion", Am J Respir Cell Mol Biol, 34(5), pp.527~536 (2006)
- Kim KC, "Role of epithelial mucins during airway infection", Pulm Pharmacol Ther, 25(6), pp.415~419 (2012)
- Martínez-Antón A, "Mucin genes have different expression patterns in healthy and diseased upper airway mucosa", Clin Exp Allergy, 36(4), pp.448~457 (2006)
- Jung JH, "Effect of Asian sand dust on mucin production in NCI-H292 cells and allergic murine model", Otolaryngol Head Neck Surg, 146(6), pp.887~894 (2012)
- 김정호, "PM10이 A549 cells에서 전염증성 cytokine발현에 미치는 영향", Tuberculosis and Respiratory Diseases, 60(6), pp.663~672 (2006), 대한결핵및호흡기학회
- Choi YS, "Asian sand dust increases MUC8 and MUC5B expressions via TLR4-dependent ERK2 and p38 MAPK in human airway epithelial cells", Am J Rhinol Allergy, 29(3), pp.161~165 (2015)
- Kim ST, "Effects of Asian sand dust on mucin gene expression and activation of nasal polyp epithelial cells", Am J Rhinol Allergy, 25(5), pp.303~306 (2011)
- Ichinose T, "The effects of microbial materials adhered to Asian sand dust on allergic lung inflammation", Arch Environ Contam Toxicol, 55, pp.348~357 (2008)
- Kim YD, "Effect of β-glucan on MUC4and MUC5B expression in human airway epithelial cells", Int Forum Allergy Rhinol, 5(8), pp.708~715 (2015)
- Chaturvedi P, "Structure, evolution, and biology of the MUC4 mucin", FASEB J, 22(4), pp.966~981 (2008)
- Lamblin G, "Human airway mucin glycosylation: a combinatory of carbohydrate determinants which vary in cystic fibrosis", Glycoconj J, 18(9), pp.661~684 (2001)
- Leikauf GD, "Mucin apoprotein expression in COPD", Chest, 121(5 Suppl), pp.166S~182S (2002)
- 배창훈, "Delphinidin Inhibits LPS-Induced MUC8 and MUC5B Expression Through Toll-like Receptor 4-Mediated ERK1", 2 and p38 MAPK in Human Airway Epithelial Cells, 2014, pp.7(3), 198~204[DOI]
- Na HG, "Spleen tyrosine kinase induces MUC5AC expression in human airway epithelial cell", Am J Rhinol Allergy, 30(2), pp.89~93 (2016)
- 배창훈, "Phorbol 12-Myristate 13-Acetate Induces MUC16 Expression via PKCδ and p38 in Human Airway Epithelial Cells", Clinical and Experimental Otorhinolaryngology, 5(3), pp.161~169 (2012), 대한이비인후과학회[DOI]