Advanced SearchSearch Tips
Suppressive Effects of Epigallocatechin Gallate Pretreatment on the Expression of Inflammatory Cytokines in RAW264.7 Cells Activated by Lipopolysaccharide
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : Journal of Life Science
  • Volume 25, Issue 9,  2015, pp.961-969
  • Publisher : Korean Society of Life Science
  • DOI : 10.5352/JLS.2015.25.9.961
 Title & Authors
Suppressive Effects of Epigallocatechin Gallate Pretreatment on the Expression of Inflammatory Cytokines in RAW264.7 Cells Activated by Lipopolysaccharide
Seo, Eun Ji; Go, Jun; Kim, Ji Eun; Koh, Eun Kyoung; Song, Sung Hwa; Sung, Ji Eun; Park, Chan Kyu; Lee, Hyun Ah; Kim, Dong Seob; Son, Hong Joo; Lee, Cung Yeoul; Lee, Hee Seob; Hwang, Dae Youn;
  PDF(new window)
Epigallocatechin gallate (EGCG), the main catechin in green tea, has been shown to have some beneficial effects against various human diseases, including diabetes, neurodegenerative disorders, cancer, cardiovascular disease and obesity. To investigate the mechanism of the suppressive effects of EGCG on inflammatory response in macrophages, alterations on the levels of nitric oxide (NO) regulatory factors and inflammatory cytokines were measured in lipopolysaccharide (LPS)-activated RAW264.7 cells. No significant toxicity was detected in RAW264.7 cells treated with 100–400 μM EGCG. Moreover, the optimal concentration of LPS was determined to be 1 μg/ml based on the results of cell viability assay, NO assay and IL-6 enzyme-linked immunsorbent assay (ELISA). Furthermore, NO levels decreased significantly by 68.2% in the 400 μM EGCG/LPS treated group, while the level of inducible nitric oxide synthase (iNOS) expression decreased by 12-17% in the 200 and 400 μM EGCG/LPS treated group. A significant decrease in transcription of pro-inflammatory cytokines (TNF- α and IL-1β) and anti-inflammatory cytokine (IL-10) was also detected in the EGCG/LPS treated group. However, IL-6 transcript and protein was maintained at a constant level when in the LPS treated group relative to the EGCG/LPS treated group. Overall, these results suggest that the differential regulation of inflammatory cytokines is an important factor influencing the suppressive effects of EGCG against LPS-activated inflammatory response in RAW264.7 cells.
Cytokines;Epigallocatechin gallate (EGCG);inflammatory response;lipopolysaccharide;nitric oxide;
 Cited by
Bae, H. B., Li, M., Kim, J. P., Kim, S. J., Jeong, C. W., Lee, H. G., Kim, W. M., Kim, H. S. and Kwak, S. H. 2009. The effect of epigallocatechin gallate on lipopolysaccharide- induced acute lung injury in a murine model. Inflammation 33, 82-91.

Beutler, B. 2002. LPS in microbial pathogenesis: promise and fulfillment. J. Endotoxin Res. 8, 329-335.

Dagmar, E. E., Jan, B., Annett, B., Martin, H., Laura, M., Rudi, L., Sabine, E., Annalisa, P. and Erich, E., W. 2008. EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Nat. Struct. Mol. Biol. 15, 558- 566. crossref(new window)

Dinarello, C. A. 2000. Proinflammatory cytokines. Chest 118, 503-508. crossref(new window)

Dragicevic, N., Smith, A., Lin, X., Yuan, F., Copes, N., Delic, V., Tan, J., Cao, C., Shytle, R. D. and Bradshaw, P. C. 2011. Green tea epigallocatechin-3-gallate (EGCG) and other flavonoids reduce Alzheimer’s amyloid-induced mitochondrial dysfunction. J. Alzheimers Dis. 26, 507-521.

Green, S. J., Nacy, C. A., Schreiber, R. D., Granger, D. L., Crawford, R. M., Meltzer, M. S. and Fortier, A. H. 1993. Neutralization of gamma interferon and tumor necrosis factor alpha blocks in vivo synthesis of nitrogen oxides from L-arginine and protection against Francisella tularensis infection in Mycobacterium bovis BCG-treated mice. Infect. Immun. 61, 689-698.

Hashimoto, K. and Sakagami, H. 2008. Induction of apoptosis by Epigallocatechin gallate and autophagy inhibitors in a mouse macrophage-like cell line. Anticancer Res. 28, 1713-1718.

Higdon, J. V. and Frei, B. 2003. Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions. Crit. Rev. Food Sci. Nutr. 43, 89-143. crossref(new window)

Hou, Y. C., Janczuk, A. and Wang, P. G. 1999. Current trends in the development of nitric oxide donors. Curr. Pharm. Des. 5, 417-441.

Ichikawa, D., Matusui, A., Imai, M., Sonoda, Y. and Kasahara, T. 2004. Effect of various catechins on the IL-12p40 production by murine peritoneal macrophages and a macrophage cell line, J774.1. Biol. Pharm. Bull. 27, 1353-1358. crossref(new window)

Kamijo, R., Gerecitano, J., Shapiro, D., Green, S. J., Aguet, M., Le, J. and Vilcek, J. 1995. Generation of nitric oxide and clearance of interferon-gamma after BCG infection are impaired in mice that lack the interferon-gamma receptor. J. Inflamm. 46, 23-31.

Khan, N., Afaq, F., Saleem, M., Ahmad, N. and Mukhtar, H. 2006. Targeting multiple signaling pathways by green tea polyphenol (-)-epigallocatechin-3-gallate. Cancer Res. 66, 2500-2505. crossref(new window)

Kim, M. K., Jung, H. S., Yoon, C. S., Kwon, M. J., Koh, K. S., Rhee, B. D. and Park, J. H. 2008. The protective effect of EGCG on INS-1 cell in the oxidative stress and mechanism. Kor. Diabetes J. 32, 121-130. crossref(new window)

Lee, S. J., Kang, H. Y., Lee, S. Y. and Hur, S. J. 2014. Green tea polyphenol Epigallocatechin-3-O-gallate attenuates lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells. J. Food Nutr. Res. 2, 425-428. crossref(new window)

Lin, Y. L. and Lin, J. K. 1997. (-)-Epigallocatechin-3-gallate blocks the induction of nitric oxide synthase by down-regulating lipopolysaccharide-induced activity of transcription factor nuclear factor-kappa B. Mol. Pharmacol. 52, 465-472.

Macedo, J. A., Ferreira, L. R., Camara, L. E., Santos, J. C., Gambero, A., Macedo, G. A. and Ribeiro, M. L. 2012. Chemopreventive potential of the tannase-mediated biotransformation of green tea. Food Chem. 133, 358-365. crossref(new window)

Masuda, M., Suzui, M. and Weinstein, I. B. 2001. Effects of epigallocatechin-3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines. Clin. Cancer Res. 7, 4220-4229.

Netsch, M. I., Gutmann, H., Aydogan, C. and Drewe, J. 2006. Green tea extract induces interleukin-8 (IL-8) mRNA and protein expression but specifically inhibits IL-8 secretion in caco-2 cells. Planta. Med. 72, 697-702. crossref(new window)

Opal, S. M. and Depalo, V. A. 2000. Anti-inflammatory cytokines. Chest 117, 1162-1172. crossref(new window)

Peng, G., Wargovich, M. J. and Dixon, D. A. 2006. Anti-proliferative effects of green tea polyphenol EGCG on Ha-Ras-induced transformation of intestinal epithelial cells. Cancer Lett. 238, 260-270. crossref(new window)

Rietschel, E. T., Kirikae, T., Schade, F. U., Mamat, U., Schmidt, G., Loppnow, H., Ulmer, A. J., Zähringer, U., Seydel, U. and Padova, F. D. 1994. Bacterial endotoxin: molecular relationships of structure to activity and function. FASEB J. 8, 217-225.

Sachinidis, A., Seul, C., Seewald, S., Ahn, H., Ko, Y. and Vetter, H. 2000. Green tea compounds inhibit tyrosine phosphorylation of PDGF β-receptor and transformation of A172 human glioblastoma. FEBS Lett. 471, 51-55. crossref(new window)

Scheller, J., Chalaris, A., Schmidt-Arras, D, and Rose-John, S. 2011. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim. Biophys. Acta. 1813, 878-888. crossref(new window)

Shankar, S., Ganapathy, S., Hingorani, S. R. and Srivastava, R. K. 2008. EGCG inhibits growth, invasion, angiogenesis and metastasis of pancreatic cancer. Front. Biosci. 13, 440-452. crossref(new window)

Singh, B. N., Shankar, S. and Srivastava, R. K. 2011. Green tea catechin, epigallocatechin-3-gallate (EGCG): Mechanisms, perspectives and clinical applications. J. Biochem. Pharmacol. Res. 82, 1807-1821. crossref(new window)

Stewart, I., Schluter, P. J. and Shaw, G. R. 2006. Cyanobacterial lipopolysaccharides and human health-a review. Environ. Health 5, 7 crossref(new window)

Tsuneki, H., Ishizaka, M., Terasawa, M., Wu, J. B., Sasaoko, T. and Kimura, I. 2004. Effect of green tea on blood glucose levels and serum proteomic patterns in diabetic (db/db) mice and on glucose metabolism in healthy humans. BMC Pharmacol. 4, 18. crossref(new window)

Waltner-Law, M. E., Wang, X. L., Law, B. K., Hall, R. K. and Nawano, M. 2002. Epigallocatechin gallate, a constituent of green tea represses hepatic glucose production. J. Biol. Chem. 277, 34933-34940. crossref(new window)

Wu, L. Y., Juan, C. C., Ho, L. T., Hsu, Y. P. and Hwang, L. S. 2004. Effect of green tea supplementation on insulin sensitivity in Sprague-Dawley rats. J. Agric. Food Chem. 52, 643-648. crossref(new window)

Yang, G. Y., Liao, J., Li, C., Chung, J., Yurkow, E. J., Ho, C. T. and Yang, C. S. 2000. Effect of black and green tea polyphenols on c-jun phosphorylation and H2O2 production in transformed and non-transformed human bronchial cell lines: possible mechanisms of cell growth inhibition and apoptosis induction. Carcinogenesis 21, 2035-2039. crossref(new window)

Yun, H. J., Yoo, W. H., Han, M. K., Lee, Y. R., Kim, J. S. and Lee, S. I. 2008. Epigallocatechin-3-gallate suppresses TNF-α-induced production of MMP-1 and -3 in rheumatoid arthritis synovial fibroblasts. Rheumatol. Int. 29, 23-29. crossref(new window)