사람 호흡기 상피세포에서 Protopanaxadiol의 Lipopolysaccharide로 유도된 활성산소 생성과 MUC5AC 과발현 억제 효과
Inhibitory Effects of Protopanaxadiol on Lipopolysaccharide-Induced Reactive Oxygen Species Production and MUC5AC Expression in Human Airway Epithelial Cells
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Background and Objectives MUC5AC is one of the major secretory mucin genes in thehuman airway epithelium. MUC5AC expression is increased by a variety of inflammatory mediators. Protopanaxadiol (PPD), one of the major active metabolites in ginseng, is known to haveanti-inflammatory, antitumor and antioxidant properties. However, the effects of PPD on mucinsecretion of airway epithelial cells still have not been reported. Therefore, the aim of this studyis to investigate the effect of PPD on lipopolysaccharide (LPS)-induced MUC5AC expressionin human airway epithelial cells. Materials and Method In the mucin-producing human NCI-H292 airway epithelial cells,the effect of PPD on MUC5AC expression was investigated using reverse transcription-polymerasechain reaction and enzyme immunoassay after treated with LPS. N-acetylcysteine (NAC)as a reactive oxygen species (ROS) scavenger, and apocynin as a nicotinamide adenine dinucleotidephosphate oxidase inhibitor were used to compare the inhibitory effect of PPD on LPSinducedROS production in human NCI-H292 cells. Results LPS significantly increased MUC5AC mRNA expression and protein production. LPS also increased ROS production. PPD inhibited LPS-induced MUC5AC mRNA expressionand protein production as well as ROS production. In addition, NAC and apocynin inhibitedLPS-induced MUC5AC mRNA expression and protein production. Conclusion These results demonstrate that PPD inhibits LPS-induced MUC5AC expressionvia ROS in human airway epithelial cells and the inhibitory effect of PPD was similar to that ofNAC and apocynin. These findings indicate that PPD may be a therapeutic agent for control ofmucus secretion and oxidative stress in human airway epithelial cells.
Abstract
Background and Objectives MUC5AC is one of the major secretory mucin genes in thehuman airway epithelium. MUC5AC expression is increased by a variety of inflammatory mediators. Protopanaxadiol (PPD), one of the major active metabolites in ginseng, is known to haveanti-inflammatory, antitumor and antioxidant properties. However, the effects of PPD on mucinsecretion of airway epithelial cells still have not been reported. Therefore, the aim of this studyis to investigate the effect of PPD on lipopolysaccharide (LPS)-induced MUC5AC expressionin human airway epithelial cells. Materials and Method In the mucin-producing human NCI-H292 airway epithelial cells,the effect of PPD on MUC5AC expression was investigated using reverse transcription-polymerasechain reaction and enzyme immunoassay after treated with LPS. N-acetylcysteine (NAC)as a reactive oxygen species (ROS) scavenger, and apocynin as a nicotinamide adenine dinucleotidephosphate oxidase inhibitor were used to compare the inhibitory effect of PPD on LPSinducedROS production in human NCI-H292 cells. Results LPS significantly increased MUC5AC mRNA expression and protein production. LPS also increased ROS production. PPD inhibited LPS-induced MUC5AC mRNA expressionand protein production as well as ROS production. In addition, NAC and apocynin inhibitedLPS-induced MUC5AC mRNA expression and protein production. Conclusion These results demonstrate that PPD inhibits LPS-induced MUC5AC expressionvia ROS in human airway epithelial cells and the inhibitory effect of PPD was similar to that ofNAC and apocynin. These findings indicate that PPD may be a therapeutic agent for control ofmucus secretion and oxidative stress in human airway epithelial cells.
참고문헌 (21)
- Oh SJ, "Ginsenoside rb2 attenuates UV-B radiationinduced reactive oxygen species and matrix metalloproteinase-2 through upregulation of antioxidant components in human dermal fibroblasts", Pharmacology, 96(1-2), pp.32~40 (2015)
- Oh SJ, "Suppressive properties of ginsenoside Rb2, a protopanaxadiol-type ginseng saponin, on reactive oxygen species and matrix metalloproteinase-2 in UV-B-irradiated human dermal keratinocytes", Biosci Biotechnol Biochem, 79(7), pp.1075~1081 (2015)
- Bai L, "Therapeutic potential of ginsenosides as an adjuvant treatment for diabetes", Front Pharmacol, 423(9), pp.1~14 (2018)
- Shergis JL, "Therapeutic potential of Panax ginseng and ginsenosides in the treatment of chronic obstructive pulmonary disease", Complement Ther Med, 22(5), pp.944~953 (2014)
- Liu J, "Role of IL-13Rα2 in modulating IL-13-induced MUC5AC and ciliary changes in healthy and CRSwNP mucosa", Allergy, 73(8), pp.1673~1685 (2018)
- Ali MS, "Upper airway mucin gene expression : A review", Laryngoscope, 117(5), pp.932~938 (2007)
- Fischer BM, "Neutrophil elastase induces MUC5AC gene expression in airway epithelium via a pathway involving reactive oxygen species", Am J Respir Cell Mol Biol, 26(4), pp.447~452 (2002)
- 김훈성, "호흡기 상피세포에서 MUC5AC와 MUC5B 발현에 대한 Betulinic Acid의 효과", 대한이비인후-두경부외과학회지, 57(8), pp.526~532 (2014), 대한이비인후과학회[DOI]
- 안지훈, "호흡기 상피세포에서 MUC5AC와 MUC5B 발현에 대한 다중벽 탄소나노튜브의 효과", 대한이비인후-두경부외과학회지, 58(8), pp.552~557 (2015), 대한이비인후과학회[DOI]
- Lee JG, "Expression and regulation of MUC8 & MUC5AC by various cytokines in normal human nasal epithelial cells", Korean J Otorhinolaryngol-Head Neck Surg, 44(6), pp.600~605 (2001)
- 김용대, "호흡기 상피 암세포에서 PKC-ERK", p38-COX-2-PGE2의 활성화를 통한 Interleukin-1β에 의한 MUC5AC 점액유전자의 발현과 점액 생성, 2003, pp.46(1), 27~34[DOI]
- Ben-Eltriki M, "20(S)-protopanaxadiol regio-selectively targets androgen receptor : Anticancer effects in castration-resistant prostate tumors", Oncotarget, 9(30), pp.20965~20978 (2018)
- Chen T, "Functional mechanism of ginsenosides on tumor growth and metastasis", Saudi J Biol Sci, 25(5), pp.917~922 (2018)
- Li J, "Mechanism of antidiabetic and synergistic effects of ginseng polysaccharide and ginsenoside Rb1 on diabetic rat model", J Pharm Biomed Anal, 158, pp.451~460 (2018)
- 김지혜, "Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases", Journal of Ginseng Research, 41(4), pp.435~443 (2017), 고려인삼학회[DOI]
- Joh EH, "Ginsenoside Rb1 and its metabolite compound K inhibit IRAK-1 activation--the key step of inflammation", Biochem Pharmacol, 82(3), pp.278~286 (2011)
- Sodrul IMD, "Role of ginsenosides in reactive oxygen species-mediated anticancer therapy", Oncotarget, 9(2), pp.2931~2950 (2017)
- Wiegman CH, "Oxidative stress-induced mitochondrial dysfunction drives inflammation and airway smooth muscle remodeling in patients with chronic obstructive pulmonary disease", J Allergy Clin Immunol, 136(3), pp.769~780 (2015)
- Na HG, "Allethrin and prallethrin stimulates MUC5AC expression through oxidative stress in human airway epithelial cells", Biochem Biophys Res Commun, 503(1), pp.316~322 (2018)
- Smirnova MG, "LPS up-regulates mucin and cytokine mRNA expression and stimulates mucin and cytokine secretion in goblet cells", Cell Immunol, 221(1), pp.42~49 (2003)
- Hsu HY, "Lipopolysaccharide-mediated reactive oxygen species and signal transduction in the regulation of interleukin-1 gene expression", J Biol Chem, 277(25), pp.22131~22139 (2002)