The Liquid Panax ginseng Inhibits Epidermal Growth factor–induced metalloproteinase 9 and cyclooxygenase 2 expressions via inhibition of inhibitor factor kappa-B-alpha and extracellular signal-regulated kinase in NCI-H292 human airway epithelial cells
Restricted accessResearch articleFirst published online March, 2011
The Liquid Panax ginseng Inhibits Epidermal Growth factor–induced metalloproteinase 9 and cyclooxygenase 2 expressions via inhibition of inhibitor factor kappa-B-alpha and extracellular signal-regulated kinase in NCI-H292 human airway epithelial cells
Ginseng (Panax ginseng C.A. Meyer) has been used in Asian countries for the treatment of various diseases. However, the mechanisms of liquid Panax ginseng (LG) on allergic inflammatory response in epidermal growth factor (EGF)–stimulated human airway epithelial cells remain largely unclear.
Methods
MUC5AC, cyclooxygenase (COX) 2, and matrix metalloproteinase (MMP) 9 expressions were measured using reverse transcription-polymerase chain reaction, Western blotting, and gelatin zymogram analyses in NCI-H292 cells. Extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) protein levels were analyzed by Western blotting.
Results
To gain insight into the antiallergy effects of LG, we examined its influence on epidermal growth factor (EGF)–induced MMP-9 and COX-2 productions in NCI-H292 cells. LG was treated for 1 hour and then followed by EGF treatment for 24 hours into NCI-H292 cells. The decrease of COX-2 production was correlated with the reduced levels of proteins and mRNAs of inducible MMP-9 and MUC5AC. LG blocked upstream signaling of NF-kappa-B activation via inhibition of phosphorylations of inhibitor factor-kappa- B-alpha (I-kappa-B-alpha) and ERK. These results suggest that LG protects NCI-H292 cells from EGF-induced damage by down-regulation of COX-2, MMP-9, and MUC5AC gene expressions by blocking NF-kappa-B and ERK.
Conclusion
LG modulates allergic inflammatory response in EGF-stimulated NCI-H292 human airway epithelial cells via inhibition of I-kappa-B-alpha and ERK.
ChooM.K., SakuraiH., KimD.H., and SaikiI.A ginseng saponin metabolite suppresses tumor necrosis factor-alpha-promoted metastasis by suppressing nuclear factor-kappaB signaling in murine colon cancer cells.Oncol Rep19: 595–600, 2008.
3.
BaeE.A., HanM.J., ShinY.W., and KimD.H.Inhibitory effects of Korean red ginseng and its genuine constituents ginsenosides Rg3, Rf, and Rh2 in mouse passive cutaneous anaphylaxis reaction and contact dermatitis models.Biol Pharm Bull29: 1862–1867, 2006.
4.
NiW., ZhangX., WangB.Antitumor activities and immunomodulatory effects of ginseng neutral polysaccharides in combination with 5-fluorouracil.J Med Food13: 270–277.
5.
ChoiK.T.Botanical characteristics, pharmacological effects and medicinal components of Korean Panax ginseng C A Meyer.Acta Pharmacol Sin29: 1109–1118, 2008.
6.
ChoiR.C., ZhuJ.T., LeungK.W.A flavonol glycoside, isolated from roots of Panax notoginseng, reduces amyloid-beta-induced neurotoxicity in cultured neurons: Signaling transduction and drug development for Alzheimer's disease.J Alzheimers Dis19: 795–811.
7.
GengJ., PengW., HuangY., FanH., LiS.Ginsenoside-Rg1 from Panax notoginseng prevents hepatic fibrosis induced by thioacetamide in rats.Eur J Pharmacol634: 162–169.
8.
SuW., SunA.J., XuD.L.Inhibiting effects of total saponins of panax ginseng on immune maturation of dendritic cells induced by oxidized-low density lipoprotein.Cell Immunol263: 99–104.
9.
PurevM., KimY.J., KimM.K.Isolation of a novel catalase (Cat1) gene from Panax ginseng and analysis of the response of this gene to various stresses.Plant Physiol Biochem48: 451–460.
YuanH.D., and ChungS.H.Protective effects of fermented ginseng on streptozotocin-induced pancreatic beta-cell damage through inhibition of NF-kappaB.Int J Mol Med25: 53–58.
12.
ZhuJ.R., TaoY.F., LouS., and WuZ.M.Protective effects of ginsenoside Rb(3) on oxygen and glucose deprivation-induced ischemic injury in PC12 cells.Acta Pharmacol Sin31: 273–280.
13.
PengX.D., DaiL.L., HuangC.Q.Relationship between anti-fibrotic effect of Panax notoginseng saponins and serum cytokines in rat hepatic fibrosis.Biochem Biophys Res Commun388: 31–34, 2009.
14.
BabayigitA., OlmezD., KaramanO.Ginseng ameliorates chronic histopathologic changes in a murine model of asthma.Allergy Asthma Proc29: 493–498, 2008.
15.
KimJ.H., ChangJ.H., YoonJ.H.[6]-Gingerol suppresses interleukin-1 beta-induced MUC5AC gene expression in human airway epithelial cells.Am J Rhinol Allergy23: 385–391, 2009.
16.
ChangJ.H., SongK.J., KimH.J.Dietary polyphenols affect MUC5AC expression and ciliary movement in respiratory cells and nasal mucosa.Am J Rhinol Allergy24: e59–e62.
17.
KimY.D., KwonE.J., ParkD.W.Interleukin-1beta induces MUC2 and MUC5AC synthesis through cyclooxygenase-2 in NCI-H292 cells.Mol Pharmacol62: 1112–1118, 2002.
18.
ChenJ.J., HuangW.C., and ChenC.C.Transcriptional regulation of cyclooxygenase-2 in response to proteasome inhibitors involves reactive oxygen species-mediated signaling pathway and recruitment of CCAAT/enhancer-binding protein delta and CREB-binding protein.Mol Biology Cell16: 5579–5591, 2005.
19.
ChenC.C., SunY.T., ChenJ.J., and ChiuK.T.TNF-alpha-induced cyclooxygenase-2 expression in human lung epithelial cells: Involvement of the phospholipase C-gamma 2, protein kinase C-alpha, tyrosine kinase, NF-kappa B-inducing kinase, and I-kappa B kinase 1/2 pathway.J Immunol165: 2719–2728, 2000.
20.
GrayT., NettesheimP., LoftinC.Interleukin-1beta-induced mucin production in human airway epithelium is mediated by cyclooxygenase-2, prostaglandin E2 receptors, and cyclic AMP-protein kinase A signaling.Mol Pharmacol66: 337–346, 2004.
21.
KimJ.H., LeeS.Y., BakS.M.Effects of matrix metalloproteinase inhibitor on LPS-induced goblet cell metaplasia.Am J Physiol287: L127–L133, 2004.
22.
WangY., ShenY., LiK.Role of matrix metalloproteinase-9 in lipopolysaccharide-induced mucin production in human airway epithelial cells.Arch Biochem Biophys486: 111–118, 2009.
23.
BinkerM.G., Binker-CosenA.A., RichardsD.LPS-stimulated MUC5AC production involves Rac1-dependent MMP-9 secretion and activation in NCI-H292 cells.Biochem Biophys Res Commun386: 124–129, 2009.
24.
HarringtonL.S., LucasR., McMasterS.K.COX-1, and not COX-2 activity, regulates airway function: Relevance to aspirin-sensitive asthma.FASEB J22: 4005–4010, 2008.
25.
ShaoM.X., UekiI.F., and NadelJ.A.Tumor necrosis factor alpha-converting enzyme mediates MUC5AC mucin expression in cultured human airway epithelial cells.Proc Natl Acad Sci USA100: 11618–11623, 2003.
26.
DeshmukhH.S., CaseL.M., WesselkamperS.C.Metalloproteinases mediate mucin 5AC expression by epidermal growth factor receptor activation.Am J Respir Crit Care Med171: 305–314, 2005.
27.
BurgelP.R., and NadelJ.A.Roles of epidermal growth factor receptor activation in epithelial cell repair and mucin production in airway epithelium.Thorax59: 992–996, 2004.
28.
NashS.P., and HeuertzR.M.Blockade of p38 map kinase inhibits complement-induced acute lung injury in a murine model.Int Immunopharmacol5: 1870–1880, 2005.
29.
ChoiH.S., ChoM.C., LeeH.G., and YoonD.Y.Indole-3-carbinol induces apoptosis through p53 and activation of caspase-8 pathway in lung cancer A549 cells.Food Chem Toxicol48: 883–890.
30.
LeberT.M., and BalkwillF.R.Zymography: A single-step staining method for quantitation of proteolytic activity on substrate gels.Anal Biochem249: 24–28, 1997.
RogerT., BresserP., SnoekM.Exaggerated IL-8 and IL-6 responses to TNF-alpha by parainfluenza virus type 4-infected NCI-H292 cells.Am J Physiol287: L1048–L1055, 2004.
33.
SaitoK., IwashitaJ., MurataJ., and AbeT.The tyrosine kinase inhibitor AG490 inhibits growth of cancer cells and activates ERK in LS174T and HT-29 cells.Anticancer Res26: 1085–1090, 2006.
34.
ChenC.C., SunY.T., ChenJ.J., and ChangY.J.Tumor necrosis factor-alpha-induced cyclooxygenase-2 expression via sequential activation of ceramide-dependent mitogen-activated protein kinases, and IkappaB kinase 1/2 in human alveolar epithelial cells.Mol Pharmacol59: 493–500, 2001.
35.
MataM., SarriaB., BuenestadoA.Phosphodiesterase 4 inhibition decreases MUC5AC expression induced by epidermal growth factor in human airway epithelial cells.Thorax60: 144–152, 2005.
36.
ItatsuK., SasakiM., YamaguchiJ.Cyclooxygenase-2 is involved in the up-regulation of matrix metalloproteinase-9 in cholangiocarcinoma induced by tumor necrosis factor-alpha.Am J Pathol174: 829–841, 2009.
