人参皂苷Rg1 通过作用于炎性因子和糖皮质激素受体减少金葡菌对肺上皮细胞的损伤

doi:10.5246/jcps.2011.03.033

人参皂苷Rg1 通过作用于炎性因子和糖皮质激素受体减少金葡菌对肺上皮细胞的损伤

袁梽漪, 孟甄, 柴玉爽, 兰嘉琦, 雷帆, 李慧颖, 邢东明, 李慧玉, 杜力军^*

清华大学教育部蛋白质科学重点实验室; 清华大学医学院生命科学学院药物药理研究室, 北京 100084

收稿日期:2011-01-03 修回日期:2011-03-25 出版日期:2011-05-06 发布日期:2011-05-06
通讯作者: 杜力军*

Ginsenoside Rg1 reduced the invasion of S. aureus into respiratory epithelial cells involving pro-inflammatory cytokines and glucocorticoid receptor

Zhi-Yi Yuan, Zhen Meng, Yu-Shuang Chai, Jia-Qi Lan, Fan Lei, Hui-Ying Li, Dong-Ming Xing, Hui-Yu Li, Li-Jun Du^*

Protein Science Laboratory of the Ministry of Education; Laboratory of Pharmaceutical Sciences, School of Medicine and School of Life Science, Tsinghua University, Beijing 100084, China

Received:2011-01-03 Revised:2011-03-25 Online:2011-05-06 Published:2011-05-06
Contact: Li-Jun Du*

摘要/Abstract

摘要：

本文旨在探讨人参皂苷Rg1体外对金葡菌感染肺上皮细胞所致病变的作用及其可能的机制。实验采用体外大鼠原代肺上皮细胞感染模型。RT-PCR和Western blot方法观察肺细胞中integrin β1, NF-κB 和糖皮质激素受体(GR)等相关因子的表达。结果表明人参皂苷Rg1可以明显抑制金葡菌感染后肺上皮细胞整合素integrin β1的表达, 下调炎性因子NF-κB, ICAM-1, TNF-α, IL-2 和 IL-6, 上调GR的表达。人参皂苷Rg1可以明显抑制金葡菌感染肺上皮细胞后的炎性因子, 从而对肺脏起到一定的保护作用。

关键词: 金黄色葡萄球菌, 人参皂苷Rg1, 肺上皮细胞

Abstract:

The invasion of Staphylococcus aureus into respiratory epithelial cells and the followed inflammatory responses cause serious tissue damage. The aim of this study was to investigate the effects of ginsenoside Rg1 (Rg1) on S. aureus infection in vitro and its action mechanism. An internalization model was constructed to determine the effect of Rg1 on S. aureus invasion. The changes of expression of integrin β1, NF-κB and glucocorticoid receptor were analyzed by Western blot. Expression of pro-inflammatory genes was validated using RT-PCR. The results demonstrated that Rg1 treatment could reduce the invasion of S. aureus into rat pulmonary epithelial cells by down-regulating integrin β1. Its anti-inflammatory action was exerted through reducing NF-κB and expressions of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2) and interleukin-6 (IL-6). The increased expression of glucocorticoid receptor was involved in this regulation. The results suggested that Rg1 could play a positive role in reducing S. aureus infections. Rg1 could be used for the treatment of S. aureus infection, potentially.

Key words: Staphylococcus aureus, Ginsenoside Rg1, Pulmonary epithelial cell

中图分类号:

Supporting:

Foundation items: National Natural Science Foundation of China (Grant No. 30973896, 30801523 and 81073092), the National S&T Major Special Project for New Drug R&D of China (Grant No. 2009ZX09103-301, 2009ZX09502 and 2011ZX09101-002-11).
^*Corresponding author. Tel./fax: 86-10-62773630

袁梽漪, 孟甄, 柴玉爽, 兰嘉琦, 雷帆, 李慧颖, 邢东明, 李慧玉, 杜力军^*. 人参皂苷Rg1 通过作用于炎性因子和糖皮质激素受体减少金葡菌对肺上皮细胞的损伤[J]. , DOI: 10.5246/jcps.2011.03.033.

Zhi-Yi Yuan, Zhen Meng, Yu-Shuang Chai, Jia-Qi Lan, Fan Lei, Hui-Ying Li, Dong-Ming Xing, Hui-Yu Li, Li-Jun Du^* . Ginsenoside Rg1 reduced the invasion of S. aureus into respiratory epithelial cells involving pro-inflammatory cytokines and glucocorticoid receptor [J]. , DOI: 10.5246/jcps.2011.03.033.

参考文献

[1] Goerke, C.; Wolz, C. Inter. J. Med. Microbiol. 2010, 300, 520-525.
[2] Sethi, S.; Murphy, T.F. Clin. Microbiol. Rev. 2001, 14, 336-363.
[3] Burns, J.L.; Emerson, J.; Stapp, J.R.; Yim, D.L.; Krzewinski, J.; Louden, L. Clin. Infect. Dis. 1998, 27, 158-163.
[4] Almeida, R.A.; Matthews, K.R.; Cifrian, E.; Guidry, A.J.; Oliver, S.P. J. Dairy Sci. 1996, 79, 1021-1026.
[5] Bayles, K.W.; Wesson, C.A.; Liou, L.E.; Fox, L.K.; Bohach, G.A.; Trumble, W.R. Infect. Immun. 1998, 66, 336-342.
[6] Hamill, R.J.; Vann, J.M.; Proctor, R.A. Infect. Immun. 1986, 54, 833-836.
[7] Vann, J.M.; Proctor, R.A. Infect. Immun. 1987, 55, 2155-2163.
[8] Menzies, B.E.; Kourteva1, I. Infect. Immun. 1998, 66, 5994-5998.
[9] Kahl, B.C.; Goulian, M.; Wamel, van W.; Herrmann, M.; Simon, S.M.; Kaplan, G.; Peters, G.; Cheung, A.L. Infect. Immun. 2000, 68, 5385-5392.
[10] Yao, L.; Bengualid, V.; Lowy, F.D.; Gibbons, J.J.; Hatcher, V.B.; Berman, J.W. Infect. Immun. 1995, 63, 1835-1839.
[11] Bengualid, V.; Hatcher, V.B.; Diamond, B.; Blumberg, E.A.; Lowy, F.D. J. Immunol. 1990, 145, 4279-4283.
[12] Song, Z.J.; Johansen, H.K.; Faber, V.; Moser, C.; Kharazmi, A.; Rygaard, J.; HØiby, N. Antimicob. Agents Chemother. 1997, 41, 961-964.
[13] Song, Z.J.; Kharazmi, A.; Wu, H.; Faber, V.; Moser, C.; Johansen, H.K.; Rygaard, J.; HØiby, N. Clin. Diagn. Lab. Immunol. 1998, 5, 882-887.
[14] Song, Z.J.; Moser, C.; Wu, H.; Faber, V.; Kharazmi, A.; HØiby, N. J. Cys. Fib. 2003, 2, 112-119.
[15] Li, W.; Gu, C.; Zhang, H.; Awang, D.V.C.; Fitzloff, J.F.; Fong, H.H.S.; van Breeman, R.B. Anal. Chem. 2000, 72, 5417-5422.
[16] Rudakewich, M.; Ba, F.; Benishin, C.G. Planta Med. 2001, 67, 533-537.
[17] Hu, J.F.; Song, X.Y.; Chu, S.F.; Chen, J.; Ji, H.J.; Chen, X.Y.; Yuan, Y.H.; Han, N.; Zhang, J.T.; Chen, N.H. Brain Res. 2011, 1374, 8-14.
[18] Rhule, A.; Rase, B.; Smith, J.R.; Shepherd, D.M. J. Ethnopharmacol. 2008, 116, 179-186.
[19] Kim, D.H.; Moon, Y.S.; Lee, T.H.; Jung, J.S.; Suh, H.W.; Song, D.K. Neurosci. Lett. 2003, 353, 13-16.
[20] Rhule, A.; Navarro, S.; Smith, J.R.; Shepherd, D.M. J. Ethnopharmacol. 2006, 106, 121-128.
[21] Chai, Y.S.; Meng, Z.; Lan, J.Q.; Wu, H.; Lei, F.; Wan, H.J.; Yuan, Z.Y.; Xing, D.M.; Du, L.J. World Sci. Technol. 2011, 12 (in press).
[22] Rubins, J.B.; Duane, P.G.; Clawson, D.; Charboneau, D.; Young, J.; Niewoehner, D.E. Infect. Immun. 1998, 61, 1352-1358.
[23] Andrews, N.C.; Faller, D.V. Nucleic Acids Res. 1991, 19, 2499-2506.
[24] Fujioka, A.; Fukioka, T.; Ishida, Y.; Maekawa, T.; Nakamura, S. Neuroscience. 2006, 141, 907-915.
[25] Timothy, J.F.; Magnus, H. Trends Microbiol. 1998, 6, 484-488.
[26] Mongodin, E.; Cutrona, O.B.J.; Bonnet, N.; Dupuit, F.; Puchelle, E.; de Bentzmann, S. Infec. Immun. 2002, 70, 620-630.
[27] Jett, B.D.; Gilmore, M.S. Infect. Immun. 2002, 70, 4697-4700.
[28] Sinha, B.; Francois, P.; Que, Y.A.; Hussain, M.; Heilmann, C.; Moreillon, P.; Lew, D.; Krause, K.H.; Peters, G.; Herrmann, M. Infect. Immun. 2000, 68, 6871-6878.
[29] Sinha, B.; FrancËois, P.P.; NuÈûe, O.; Foti,M.; Hartford, O.M.; Vaudaux, P.; Foster, T.J.; Lew, D.P.; Herrmann, M.; Krause, K.H. Cellular Microbiol. 1999, 1, 109-117.
[30] Virtanen, I.; Tervo, K.; Korhonen, M.; Paallysaho, T.; Tervo, T. Acta Ophthalmol. 1992, 202 (Suppl.), 18-21.
[31] Schwartz, M.A. Trends Cell Biol. 2001, 11, 466-470.
[32] Kumar, A.; Zhang, J.; Yu, F.S.X. Invest. Ophthalmol. Vis. Sci. 2004, 45, 3513-3522.
[33] Peterson, M.L.; Ault, K.; Kremer, M.J.; Klingelhutz, A.J.; Davis, C.C.; Squier, C.A.; Schlievert, P.M. Infect. Immun. 2005, 73, 2164-2174.
[34] Dziarski, R.; Wang, Q.L.; Miyake, K.; Kirschning, C.J.; Gupta, D. J. Immune. 2001, 166, 1938-1944.
[35] Morrison, D.C.; Ryan, J.L. Annu. Rev. Med. 1987, 38, 417-432.
[36] Barnes, P.J.; Karin, M. The New Eng. J. Med. 1997, 336, 1066-1071.
[37] Wu, C.F.; Bi, X.L.; Yang, J.Y. Int. Immunopharmacol. 2007, 7, 313-320.
[38] Di Mango, E.; Zar, H.J.; Bryan, R.; Prince, A. J. Clin. Invest. 1995, 96, 2204-2210.
[39] Bosscher, K.D.; Berghe, W.V.; Haegeman, G. Endocr. Reviews. 2005, 24, 488-522.
[40] Scheinman, R.; Cogswell, P.C.; Lofquist, A.; Baldwin, J.A.S. Science. 1995, 270, 283-286.
[41] Leung, K.W.; Cheng, Y.K.; Mak, N.K.; Chan, K.K.C.; Fan, T.P.D.; Wong, N.S. FEBS Lett. 2006, 580, 3211-3216.
[42] Leung, K.W.; Pon, Y.L.; Wong, R.N.; Wong, A.S. J. Biol. Chem. 2006, 281, 36280-36288.