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호흡기 상피세포에서 Roflumilast에 의한 MUC5AC와 MUC5B 발현 억제

Roflumilast Attenuates MUC5AC and MUC5B Expression in Airway Epithelial Cells

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주제분류이비인후과학

초록

Background and Objectives Roflumilast, a selective inhibitor of phosphodiesterase type 4, has an anti-inflammatory property. It has been used in the treatment of chronic inflammatory airway diseases such as chronic obstructive pulmonary disease and asthma. However, the effect of roflumilast on mucus secretion in inflammatory airway epithelial cells has not been reported. Therefore, this study was aimed at investigating the effects of roflumilast on the inflammatory mediator-induced MUC5AC and MUC5B expression in human airway epithelial cells. Materials and Method In human mucin-producing NCI-H292 airway epithelial cells and primary cultures of nasal epithelial cells, the effects of roflumilast on lipopolysaccharide (LPS)- and phorbl-12-myrsitate-13-acetate (PMA)-induced MUC5AC and MUC5B expression were analyzed by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results Roflumilast attenuated LPS-induced MUC5AC and MUC5B mRNA and glycoprotein expression in NCI-H292 cells. And roflumilast attenuated PMA-induced MUC5AC and MUC5B mRNA and glycoprotein expression in NCI-H292 cells. In addition, roflumilast attenuated LPS and PMA-induced MUC5AC and MUC5B mRNA expression in the primary cultures of nasal epithelial cells. Conclusion These results suggest that roflumilast attenuates MUC5AC and MUC5B expressions in airway epithelial cells. Roflumilast may be a potentially ideal therapeutic agent for the control of mucus-hypersecretion in treating chronic inflammatory airway diseases. Korean J Otorhinolaryngol-Head Neck Surg 2014;57(12):830-5

Abstract

Background and Objectives Roflumilast, a selective inhibitor of phosphodiesterase type 4, has an anti-inflammatory property. It has been used in the treatment of chronic inflammatory airway diseases such as chronic obstructive pulmonary disease and asthma. However, the effect of roflumilast on mucus secretion in inflammatory airway epithelial cells has not been reported. Therefore, this study was aimed at investigating the effects of roflumilast on the inflammatory mediator-induced MUC5AC and MUC5B expression in human airway epithelial cells. Materials and Method In human mucin-producing NCI-H292 airway epithelial cells and primary cultures of nasal epithelial cells, the effects of roflumilast on lipopolysaccharide (LPS)- and phorbl-12-myrsitate-13-acetate (PMA)-induced MUC5AC and MUC5B expression were analyzed by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results Roflumilast attenuated LPS-induced MUC5AC and MUC5B mRNA and glycoprotein expression in NCI-H292 cells. And roflumilast attenuated PMA-induced MUC5AC and MUC5B mRNA and glycoprotein expression in NCI-H292 cells. In addition, roflumilast attenuated LPS and PMA-induced MUC5AC and MUC5B mRNA expression in the primary cultures of nasal epithelial cells. Conclusion These results suggest that roflumilast attenuates MUC5AC and MUC5B expressions in airway epithelial cells. Roflumilast may be a potentially ideal therapeutic agent for the control of mucus-hypersecretion in treating chronic inflammatory airway diseases. Korean J Otorhinolaryngol-Head Neck Surg 2014;57(12):830-5

참고문헌 (18)

  1. Ali MS, "Upper airway mucin gene expression: a review", Laryngoscope, 117(5), pp.932~938 (2007)
  2. 우현재, "호흡기 상피세포에서 roxithromycin에 의한 MUC5B와 MUC8 점액 유전자 발현 및 점액 생성의 억제", 대한이비인후과학회지 두경부외과학, 51(7), pp.617~622 (2008), 대한이비인후과학회
  3. Lee JG, "Expression and regulation of MUC8 & MUC5AC by various cytokines in normal human nasal epithelial cells", Korean J Otolaryngol-Head Neck Surg, 44(6), pp.600~605 (2001)
  4. 배창훈, "The Effect of Doxycycline on PMA-Induced MUC5B Expression via MMP-9 and p38 in NCI-H292 Cells", Clinical and Experimental Otorhinolaryngology, 4(4), pp.177~183 (2011), 대한이비인후과학회
  5. 심재정, "기도의 점액 과분비 질환에서 MUC5AC의 발현의 신호 전달 경로에 관한 연구", Tuberculosis and Respiratory Diseases, 55(1), pp.21~30 (2003), 대한결핵및호흡기학회
  6. Price D, "The use of roflumilast in COPD: a primary care perspective", Prim Care Respir J, 19(4), pp.342~351 (2010)
  7. Ishinaga H, "Effects of dexamethasone on mucin gene expression in cultured human nasal epithelial cells", Laryngoscope, 112(8 PT 1), pp.1436~1440 (2002)
  8. Jin SL, "Phosphodiesterase 4 and its inhibitors in inflammatory diseases", Chang Gung Med J, 35(3), pp.197~210 (2012)
  9. Page CP, "Selective PDE inhibitors as novel treatments for respiratory diseases", Curr Opin Pharmacol, 12(3), pp.275~286 (2012)
  10. Souness JE, "Immunosuppressive and anti-inflammatory effects of cyclic AMP phosphodiesterase (PDE) type 4 inhibitors", Immunopharmacology, 47(2-3), pp.127~162 (2000)
  11. Lipworth BJ, "Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease", Lancet, 365(9454), pp.167~175 (2005)
  12. Spina D, "PDE4 inhibitors: current status", Br J Pharmacol, 155(3), pp.308~315 (2008)
  13. Reid DJ, "Roflumilast: a novel treatment for chronic obstructive pulmonary disease", Ann Pharmacother, 46(4), pp.521~529 (2012)
  14. Kwak HJ, "Roflumilast inhibits lipopolysaccharide-induced inflammatory mediators via suppression of nuclear factor-kappaB, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase activation", J Pharmacol Exp Ther, 315(3), pp.1188~1195 (2005)
  15. Yuan-Chen Wu D, "Distinctive epidermal growth factor receptor", extracellular regulated kinase-independent and -dependent signaling pathways in the induction of airway mucin 5B and mucin 5AC expression by phorbol 12-myristate 13-acetate, 2007, pp.170(1), 20~32
  16. Bae CH, "Diallyl disulfide induces MUC5B expression via ERK2 in human airway epithelial cells", Phytother Res, 26(2), pp.197~203 (2012)
  17. Woo HJ, "Leptin up-regulates MUC5B expression in human airway epithelial cells via mitogen-activated protein kinase pathway", Exp Lung Res, 36(5), pp.262~269 (2010)
  18. Lahu G, "Pharmacokinetic evaluation of roflumilast", Expert Opin Drug Metab Toxicol, 7(12), pp.1577~1591 (2011)

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