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Effects of Luteolin on IL-1β-Induced MCP1 Protein Expression

Luteolin의 IL-1β에 의한 MCP1 단백질 발현 증가에 미치는 영향

  • Lim, Jun-Hee (Department of Immunology, School of Medicine, Keimyung University) ;
  • Kwon, Taeg-Kyu (Department of Immunology, School of Medicine, Keimyung University)
  • 임준희 (계명대학교 의과대학 면역학교실) ;
  • 권택규 (계명대학교 의과대학 면역학교실)
  • Published : 2009.04.30

Abstract

Monocyte chemoattractant protein 1 (MCP1) plays a key role in monocyte /macrophage infiltration to the sub-endothelial space of the blood vessel wall, which is a critical initial step in atherosclerosis. In this study, we examined $interleukin-1{\bate}$ ($IL-1{\beta}$) induced MCP1 expressions via activation of transcription factor $NF-{\kappa}B$ in primary human aorta smooth muscle cells. We determined the effect of several anti-inflammatory agents on $IL-1{\beta}-induced$ MCP1 expression. The pretreatment of luteolin significantly suppressed $IL-1{\beta}-induced$ MCP1 expressions through blocking activation and translocation of $NF-{\kappa}B$ to the nucleus.

혈관벽에 단핵구, 대식세포 등의 세포와 지질 등의 축적은 중요한 동맥경화 발병 요인이다. 이들 세포의 혈관벽으로의 이동에 있어서 chemokine인 MCP1이 중요한 역할을 한다는 것이 많이 알려져 있다. 본 연구에서는 사람 평활근세포에서 $IL-1{\beta}$의 처리에 의하여 MCP1의 발현이 증가되는 기전을 알아보고자 실험을 진행하였다. $IL-1{\beta}$의 처리는 전사인자 $NF-{\kappa}B$의 활성화를 통해 MCP1 발현을 전사단계에서 증가시켰다. 이러한 $IL-1{\beta}$에 의해 증가된 MCP1 발현을 억제하는 물질을 찾기 위해 여러 항염증작용을 하는 물질들을 전처리하여 확인해 본 결과 luteolin이 선택적으로 $IL-1{\beta}$에 의해 증가된 MCP1의 발현을 전사단계에서 저해하는 것을 확인하였고 이는 전사인자 $NF-{\kappa}B$가 핵으로 이동하는 것을 감소시킴으로써 나타나는 현상임을 확인하였다. Luteolin이 염증작용을 조절하는데 있어서 중요한 전사인자인 $NF-{\kappa}B$의 활성을 조절한다는 것을 본 실험을 통해 알 수 있었고 이는 식용식물에서 일반적으로 발견되는 luteolin이 어떠한 기전으로 항 염증작용을 하는지에 대한 이해를 높여줄 것이다.

Keywords

References

  1. Baek, W. K., J. W. Park, J. H. Lim, S. I. Suh, M. H. Suh, E. Gabrielson, and T. K. Kwon. 2002. Molecular cloning and characterization of the human budding uninhibited by benomyl (BUB3) promoter. Gene 295, 117-123 https://doi.org/10.1016/S0378-1119(02)00827-2
  2. Chen, C. Y., W. H. Peng, K. D. Tsai, and S. L. Hsu. 2007. Luteolin suppresses inflammation-associated gene expression by blocking NF-kappaB and AP-1 activation pathway in mouse alveolar macrophages. Life Sci. 81, 1602-1614 https://doi.org/10.1016/j.lfs.2007.09.028
  3. Comalada, M., I. Ballester, E. Bailon, S. Sierra, J. Xaus, J. Galvez, F. S. de Medina, and A. Zarzuelo. 2006. Inhibition of pro-inflammatory markers in primary bone marrow-derived mouse macrophages by naturally occurring flavonoids: analysis of the structure-activity relationship. Biochem. Pharmacol. 72, 1010-1021 https://doi.org/10.1016/j.bcp.2006.07.016
  4. Dawson, T. C., W. A. Kuziel, T. A. Osahar, and N. Maeda. 1999. Absence of CC chemokine receptor-2 reduces atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis 143, 205-211 https://doi.org/10.1016/S0021-9150(98)00318-9
  5. Gosling, J., S. Slaymaker, L. Gu, S. Tseng, C. H. Zlot, S. G. Young, B. J. Rollins, and I. F. Charo. 1999. MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B. J. Clin. Invest. 103, 773-778 https://doi.org/10.1172/JCI5624
  6. Gu, L., Y. Okada, S. K. Clinton, C. Gerard, G. K. Sukhova, P. Libby, and B. J. Rollins. 1998. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol. Cell 2, 275-281 https://doi.org/10.1016/S0021-9150(99)00342-1
  7. Jang, S., K. W. Kelley, and R. W. Johnson. 2008. Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1. Proc. Natl. Acad. Sci. USA 105, 7534-7539 https://doi.org/10.1073/pnas.0802865105
  8. Kim, E. K., K. B. Kwon, M. Y. Song, M. J. Han, J. H. Lee, Y. R. Lee, J. H. Lee, D. G. Ryu, B. H. Park, and J. W. Park. 2007. Flavonoids protect against cytokine-induced pancreatic beta-cell damage through suppression of nuclear factor kappaB activation. Pancreas. 35, e1-9
  9. Lamy, S., V. Bedard, D. Labbe, H. Sartelet, C. Barthomeuf, D. Gingras, and R. Beliveau. 2008. The dietary flavones apigenin and luteolin impair smooth muscle cell migration and VEGF expression through inhibition of PDGFR-beta phosphorylation. Cancer Prev. Res. (Phila Pa). 1, 452-459 https://doi.org/10.1158/1940-6207.CAPR-08-0072
  10. Martin, T., P. M. Cardarelli, G. C. Parry, K. A. Felts, and R. R. Cobb. 1997. Cytokine induction of monocyte chemoattractant protein-1 gene expression in human endothelial cells depends on the cooperative action of NF-kappa B and AP-1. Eur. J. Immunol. 27, 1091-1097 https://doi.org/10.1002/eji.1830270508
  11. Peters, W. and I. F. Charo. 2001. Involvement of chemokine receptor 2 and its ligand, monocyte chemoattractant protein-1, in the development of atherosclerosis: lessons from knockout mice. Curr. Opin. Lipidol. 12, 175-180 https://doi.org/10.1097/00041433-200104000-00011
  12. Rollins, B. J. and J. S. Pober. 1991. Interleukin-4 induces the synthesis and secretion of MCP-1/JE by human endothelial cells. Am. J. Pathol. 138, 1315-1319
  13. Rollins, B. J., T. Yoshimura, E. J. Leonard, and J. S. Pober. 1990. Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE. Am. J. Pathol. 136, 1229-1233
  14. Ross, R. 1993. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362, 801-809 https://doi.org/10.1038/362801a0
  15. Ross, R. 1999. Atherosclerosis--an inflammatory disease. N. Engl. J. Med. 340, 115-126 https://doi.org/10.1056/NEJM199901143400207
  16. Rossi, D. and A. Zlotnik. 2000. The biology of chemokines and their receptors. Annu. Rev. Immunol. 18, 217-242 https://doi.org/10.1146/annurev.immunol.18.1.217
  17. Sallusto, F., C. R. Mackay, and A. Lanzavecchia. 2000. The role of chemokine receptors in primary, effector, and memory immune responses. Annu. Rev. Immunol. 18, 593-620 https://doi.org/10.1146/annurev.immunol.18.1.593
  18. Sharma, V., M. Mishra, S. Ghosh, R. Tewari, A. Basu, P. Seth, and E. Sen. 2007. Modulation of interleukin-1beta mediated inflammatory response in human astrocytes by flavonoids: implications in neuroprotection. Brain Res. Bull. 73, 55-63 https://doi.org/10.1016/j.brainresbull.2007.01.016
  19. Shimoi, K., H. Okada, M. Furugori, T. Goda, S. Takase, M. Suzuki, Y. Hara, H. Yamamoto, and N. Kinae. 1998. Intestinal absorption of luteolin and luteolin 7-O-beta-glucoside in rats and humans. FEBS Lett. 438, 220-224 https://doi.org/10.1016/S0014-5793(98)01304-0
  20. Xagorari, A., A. Papapetropoulos, A. Mauromatis, M. Economou, T. Fotsis, and C. Roussos. 2001. Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine production in macrophages. J. Pharmacol. Exp. Ther. 296, 181-187
  21. Zlotnik, A. and O. Yoshie. 2000. Chemokines: a new classification system and their role in immunity. Immunity 12, 121-127 https://doi.org/10.1016/S1074-7613(00)80165-X
  22. Zoja, C., J. M. Wang, S. Bettoni, M. Sironi, D. Renzi, F. Chiaffarino, H. E. Abboud, J. Van Damme, A. Mantovani, G. Remuzzi, and A. Rambaldi. 1991. Interleukin-1 beta and tumor necrosis factor-alpha induce gene expression and production of leukocyte chemotactic factors, colony-stimulating factors, and interleukin-6 in human mesangial cells. Am. J. Pathol. 138, 991-1003

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