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DMfree®(Green Tea Extract) Inhibits IL-6 of Mycobacterium leprae Infected Mesenchymal Stem Cells

디엠프리(녹차추출물)에 의한 나균 감염 중간엽줄기세포의 IL-6 생산 억제

  • 박란숙 (숭의여자대학교 식품영양과)
  • Received : 2015.06.11
  • Accepted : 2015.08.21
  • Published : 2015.08.31

Abstract

Previous reports revealed that DMfree (green tea extract) inhibited expression of the IL-6 gene in Mycobacterium lepraeinfected MSCs (mesenchymal stem cells). This study aimed to measure IL-6, $IL-1{\beta}$, $TNF-{\alpha}$ and PGE2 production in M. leprae-infected MSCs using ELISA. To confirm the effect of DMfree on IL-6 and signal transduction, a western blotting test was performed. DMfree inhibited the expression of IL-6 in the MSCs and the heterodimer of STAT3, which also affects the expression of multiple genes. Though DMfree pre-treatment of control MSCs produced a baseline level of IL-6, it significantly inhibited the production of IL-6 in M. leprae-infected MSCs. There was no significant difference in IL-6 production between 1 and 7 day treatment groups. M. leprae-infected MSCs produced more $IL-1{\beta}$, $TNF-{\alpha}$ and PGE2, but DMfree could not inhibit their production at a physiological concentration. This is different from other reports that used higher concentration of EGCG treatment, resulting in significant inhibition of the cytokines. The inhibition appears to be related to the concentration of EGCG. These results indicate that DMfree can alleviate inflammation involving IL-6.

Keywords

References

  1. Adams L, Gillis TP, Hwang DH, Krahenbuhl JL. 1997. Effects of essential fatty acid deficiency on prostaglandin $E_2$ production and cell-mediated immunity in a mouse model of leprosy. Infect Immun 65:1152-1157
  2. Ahmed S, Marotte H, Kwan K, Ruth JL, Campbell PL, Rabquer BJ, Pakozdi A, Koch AE. 2008. Epigallocatechin-3-gallate inhibits IL-6 synthesis and suppresses transsignaling by enhancing soluble gp130 production. Proc Natl Acad Sci USA 105: 14692-14697 https://doi.org/10.1073/pnas.0802675105
  3. Akhtar N, Haqqi TM. 2011. Epigallocatechin-3-gallate suppresses the global interleukin-1beta-induced inflammatory response in human chondrocytes. Arthritis Res Therapy 13:R93 https://doi.org/10.1186/ar3368
  4. Barnett M, Cooney JM, Dommels YE, Nones K, Brewster DT, Park Z, Butts CA, McNabbWc, Laing WA, Roy NC. 2013. Modulation of colonic inflammation in Mdr1a$Mdr1a^{-/-/}$ mice by green tea polyphenols and their effects on the colon transcriptome and proteom. J Nutr Biochem 24:1678-1690 https://doi.org/10.1016/j.jnutbio.2013.02.007
  5. Chacko SM, Thambi PT, Kuttan R, Nishigaki I. 2010. Beneficial effects of green tea: A literature review. Chinese Medicine 5:13-21 https://doi.org/10.1186/1749-8546-5-13
  6. Chizzolini C, Brembilla NC. 2009. Prostaglandin $E_2$: igniting the fire. Immunol Cell Biol 87:510-511 https://doi.org/10.1038/icb.2009.56
  7. Comblain F, Sanchez C, Lesponne I, Balligand M, Serisler S, Henrotin Y. 2015. Curcuminoids extract, hydrolyzed collagen and green tea extract synergically inhibit inflammatory and catabolic mediator's synthesis by normal bovine and osteoarthritic human chondrocytes in monolayer. PLoS ONE 10:e0121654 https://doi.org/10.1371/journal.pone.0121654
  8. Hirano T, Matsuda T, Turner M, Miyasaka N, Buchan G, Tang B, Sato K, Shimizu M, Maini R, Feldmann M, Kishimoto T. 1988. Excessive production of interleukin6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol 18:1797-1801 https://doi.org/10.1002/eji.1830181122
  9. Kang TJ, Yeom JE, Lee HJ, Rho SH, Han H, Chae GT. 2004. Growth kinetics of human mesenchymal stem cells from bone marrow and umbilical cord blood. Acta Haematol 112:230-233 https://doi.org/10.1159/000081281
  10. Kang TJ, Chae GT. 2011. The role of intracellular receptor NODs for cytokine production by macrophages infected with Mycobacterium leprae. Immune Network 11:424-427 https://doi.org/10.4110/in.2011.11.6.424
  11. Kang TJ, Lee GS, Kim SK, Jin SH, Chae GT. 2010. Comparison of two mice strains, A/J and C57BL/6, in caspase-1 activity and IL-$1{\beta}$ secretion of macrophage to Mycobacterium leprae infection. Mediators Inflamm 2010:708-713
  12. Kishimoto T. 2010. IL-6: from its discovery to clinical applications. Int Immunol 22:347-352 https://doi.org/10.1093/intimm/dxq030
  13. Mattos KA, D'Avila H, Rodrigues LS, Oliveira VG, Sarno EN, Atella GC, Pereira GM, Bozza PT, Pessolani MC. 2010. Lipid droplet formation in leprosy: Toll-like receptor-regulated organelles involved in eicosanoid formation and Mycobacterium leprae pathogenesis. J Leuko Biol 87:371-384 https://doi.org/10.1189/jlb.0609433
  14. McKay DL, Blumberg JB. 2002. The role of tea in human health: An update. J Amer Coll Nutr 21:1-13 https://doi.org/10.1080/07315724.2002.10719187
  15. Nunea-Sanches MA, Gonzalez-Sarrias A, Romo-Vaquero M, Barcia-Villalba R, Selma MV, Tomas-Barberan FA, Garcia-Conesa MT, Espin JC. 2015. Dietary phenolics against colorectal cancer. From promising preclinical results to poor translation into clinical trials: Pitfalls and future needs. Mol Nutr Food Res 59:1274-1291 https://doi.org/10.1002/mnfr.201400866
  16. Oh TS, Bae EY, Kim MH, Oh HM, Lee SW, Kim CH. 2014. Inhibition of IL-6-induced STAT3 activation by pirmaradienoic acid from Aralia continentalis. Bull Korean Chem Soc 35:3661-3664 https://doi.org/10.5012/bkcs.2014.35.12.3661
  17. Parida SK, Grau GE, Zaheer SA, Mukherjee R. 1992. Serum tumor necrosis factor and interleukin 1 in leprosy and during lepra reaction. Clin Immunol Immunopathol 63:23-27 https://doi.org/10.1016/0090-1229(92)90088-6
  18. Park RS. 2014. Effect of DMfree$^{(R)}$(GTE) on gene array profile of M. leprae infected mesenchymal stem cells. Korean J Food & Nutr 27:267-273 https://doi.org/10.9799/ksfan.2014.27.2.267
  19. Riegsecker S, Wiczynski D, Kaplan MJ, Ahmed S. 2013. Potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation in rheumatoid arthritis. Life Sci 93:307-312 https://doi.org/10.1016/j.lfs.2013.07.006
  20. Sibley LD, Krahenbuhl JL. 1988. Defective activation of granuloma macrophages from Mycobacterium leprae-infected nude mice. J Leukoc Biol 43:60-66
  21. Yang EJ, Lee J, Lee SY, Kim EK, Moon YM, Jung YO, Park SH, Cho ML. 2014. EGCG attenuates autoimmune arthritis by inhibition of STAT3 and HIF-$1{\alpha}$ with TH17/Treg control. PLoS ONE 9:e86062 https://doi.org/10.1371/journal.pone.0086062
  22. Zhang S, Shan L, Li Q, Wang X, Li S, Zhang Y, Gu J, Liu X, Li H, Zhang W. 2014. Systematic analysis of the multiple bioactivities of green tea through a network pharmacology approach. Evid Based Complement Alternat Med 2014: atricle ID 512081, 11 pages