Immunomodulatory Effects of Dioscoreae Rhizome Against Inflammation through Suppressed Production of Cytokines Via Inhibition of the NF-κB Pathway
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Dioscoreae Rhizome (DR) has been used in traditional medicine to treat numerous diseases and is reported to have anti-diabetes and anti-tumor activities. To identify a bioactive traditional medicine with anti-inflammatory activity of a water extract of DR (EDR), we determined the mRNA and protein levels of proinflammatory cytokines in macrophages through RT-PCR and western blot analysis and performed a FACS analysis for measuring surface molecules. EDR dose-dependently decreased the production of NO and pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, and PGE_2, as well as mRNA levels of iNOS, COX-2, and pro-inflammatory cytokines, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as B7-1 and B7-2 was also reduced by EDR. Furthermore, activation of the nuclear transcription factor, NF-κB, but not that of IL-4 and IL-10, in macrophages was inhibited by EDR. These results show that EDR decreased pro-inflammatory cytokines via inhibition of NF-κB-dependent inflammatory protein level, suggesting that EDR could be a useful immunomodulatory agent for treating immunological diseases.
Abstract
Dioscoreae Rhizome (DR) has been used in traditional medicine to treat numerous diseases and is reported to have anti-diabetes and anti-tumor activities. To identify a bioactive traditional medicine with anti-inflammatory activity of a water extract of DR (EDR), we determined the mRNA and protein levels of proinflammatory cytokines in macrophages through RT-PCR and western blot analysis and performed a FACS analysis for measuring surface molecules. EDR dose-dependently decreased the production of NO and pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, and PGE_2, as well as mRNA levels of iNOS, COX-2, and pro-inflammatory cytokines, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as B7-1 and B7-2 was also reduced by EDR. Furthermore, activation of the nuclear transcription factor, NF-κB, but not that of IL-4 and IL-10, in macrophages was inhibited by EDR. These results show that EDR decreased pro-inflammatory cytokines via inhibition of NF-κB-dependent inflammatory protein level, suggesting that EDR could be a useful immunomodulatory agent for treating immunological diseases.
참고문헌 (26)
- Duncan, B. B., "Atherosclerosis Risk in Communities Study. 2003. Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study", Diabetes, 52, pp.1799~1805 (2003)
- Jacobs, M., "Low-grade inflammation can partly explain the association between the metabolic syndrome and either coronary artery disease or severity of peripheral arterial disease: the CODAM study", Eur. J. Clin. Invest, 39, pp.437~444 (2009)
- Vane, J. R., "Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation", Proc. Natl. Acad. Sci. USA, 91, pp.2046~2050 (1994)
- Tae Hoon Lee, "Methanol Extracts of Stewartia koreana Inhibit Cyclooxygenase-2 (COX-2) and Inducible Nitric Oxide Synthase (iNOS) Gene Expression by Blocking NF-κB Transactivation in LPS-activated RAW 264.7 Cells", Molecules and Cells, 23(3), pp.398~404 (2007), 한국분자세포생물학회
- Nathan, C., "Inducible nitric oxide synthase: what difference does it make?", J. Clin. Invest, 100, pp.2417~2423 (1997)
- Bogdan, C., "Nitric oxide and the immune response", Nat. Immunol, 2, pp.907~916 (2001)
- Vila-del Sol, V, "Involvement of TNF and NF-kappa B in the transcriptional control of cyclooxygenase- 2 expression by IFN-gamma in macrophages", J. Immunol, 174, pp.2825~2833 (2005)
- Lind, L., "Circulating markers of inflammation and atherosclerosis", Atherosclerosis, 169, pp.203~214 (2003)
- Tilg, H., "Serum levels of cytokines in chronic liver diseases", Gastroenterology, 103, pp.264~274 (1992)
- Coker, R. K., "Pulmonary fibrosis: cytokines in the balance", Eur. Respir. J, 11, pp.1218~1221 (1998)
- Siebenlist, U, "Structure, regulation and function of NF-kappa B", Annu. Rev. Cell. Biol, 10, pp.405~455 (1994)
- Renard, P, "The proinflammatory transcription factor NFkappaB: a potential target for novel therapeutical strategies", Cell. Biol. Toxicol, 15, pp.341~344 (1999)
- Tian, B., "Identification of a nuclear factor kappa B-dependent gene network", Recent. Prog. Horm. Res, 58, pp.95~130 (2003)
- Zhong, X, "Temperature dependence of seedling establishment of a perennial, Dioscorea tokoro", J. Plant. Res, 115, pp.55~57 (2002)
- Lee, S. C., "The evaluation of reno- and hepatoprotective effects of huai-shan-yao (Rhizome Dioscoreae)", Am. J. Chin. Med, 30, pp.609~616 (2002)
- Tewtrakul, S., "Nitric oxide inhibitory substances from the rhizomes of Dioscorea membranacea", J. Ethnopharmacol, 109, pp.412~416 (2007)
- Stuehr, D. J., "Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells", J. Exp. Med, 169, pp.1543~1555 (1989)
- Lee, G. I., "Inhibitory effects of oriental herbal medicines on IL-8 induction in lipopolysaccharideactivated rat macrophages", Planta. Med, 61, pp.26~30 (1995)
- Laskin, D. L, "Macrophages and inflammatory mediators in tissue injury", Annu. Rev. Pharmacol. Toxicol, 35, pp.655~677 (1995)
- Furchgott, R., "Endothelial cells as mediators of vasodilation of arteries", J. Cardiovasc. Pharmacol, 6, pp.S336~343 (1984)
- Wei, X., "Altered immune responses in mice lacking inducible nitricoxide synthase", Nature, 375, pp.408~4011 (1995)
- Ahmad, N., "Regulation of cyclooxygenase-2 by nitric oxide in activated hepatic macrophages during acute endotoxemia", J. Leukoc. Biol, 71, pp.1005~1011 (2002)
- Li, Q, "NFkappa B regulation in the immune system", Nat. Rev. Immunol, 2, pp.725~734 (2002)
- Richmond, A., "NF-kappa B, chemokine gene transcription and tumour growth", Nat. Rev. Immunol, 2, pp.664~674 (2002)
- Lee, S., "Antipinflammatory function of arctiin by inhibiting COX-2 expression via NF-kappaB pathways", Inflammation, 8, pp.16~ (2011)
- Karin, M, "Phosphorylation meets ubiquitination: The control of NF-kappa B activity", Annu. Rev. Immunol, 18, pp.621~663 (2000)