Biomolecules & Therapeutics

  • 제23권1호
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  • Pages.84-89
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  • 2015
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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7α-Hydroxycholesterol Elicits TLR6-Mediated Expression of IL-23 in Monocytic Cells

  • Seo, Hyun Chul (Department of Pharmacology, Pusan National University - School of Medicine) ;
  • Kim, Sun-Mi (Department of Pharmacology, Pusan National University - School of Medicine) ;
  • Eo, Seong-Kug (College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University) ;
  • Rhim, Byung-Yong (Department of Pharmacology, Pusan National University - School of Medicine) ;
  • Kim, Koanhoi (Department of Pharmacology, Pusan National University - School of Medicine)
  • 투고 : 2014.06.05
  • 심사 : 2014.09.01
  • 발행 : 2015.01.01
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초록

We investigated the question of whether 7-oxygenated cholesterol derivatives could affect inflammatory and/or immune responses in atherosclerosis by examining their effects on expression of IL-23 in monocytic cells. $7{\alpha}$-Hydroxycholesterol ($7{\alpha}OHChol$) induced transcription of the TLR6 gene and elevated the level of cell surface TLR6 protein in THP-1 monocytic cells. Addition of an agonist of TLR6, FSL-1, to TLR6-expressing cells by treatment with $7{\alpha}OHChol$ resulted in enhanced production of IL-23 and transcription of genes encoding the IL-23 subunit ${\alpha}$ (p19) and the IL-12 subunit ${\beta}$ (p40). However, treatment with 7-ketocholesterol (7K) and $7{\beta}$-hydroxycholesterol ($7{\beta}OHChol$) did not affect TLR6 expression, and addition of FSL-1 to cells treated with either 7K or $7{\beta}OHChol$ did not influence transcription of the genes. Pharmacological inhibition of ERK, Akt, or PI3K resulted in attenuated transcription of TLR6 induced by $7{\alpha}OHChol$ as well as secretion of IL-23 enhanced by $7{\alpha}OHChol$ plus FSL-1. Inhibition of p38 MAPK or JNK resulted in attenuated secretion of IL-23. These results indicate that a certain type of 7-oxygenated cholesterol like $7{\alpha}OHChol$ can elicit TLR6-mediated expression of IL-23 by monocytic cells via PI3K/Akt and MAPKs pathways.

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참고문헌

  1. Aggarwal, S., Ghilardi, N., Xie, M. H., de Sauvage, F. J. and Gurney, A. L. (2003) Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J. Biol. Chem. 278, 1910-1914. https://doi.org/10.1074/jbc.M207577200
  2. Brown, A. J. and Jessup, W. (1999) Oxysterols and atherosclerosis. Atherosclerosis 142, 1-28. https://doi.org/10.1016/S0021-9150(98)00196-8
  3. Brown, A. J., Leong, S. L., Dean, R. T. and Jessup, W. (1997) 7-Hydroperoxycholesterol and its products in oxidized low density lipoprotein and human atherosclerotic plaque. J. Lipid Res. 38, 1730-1745.
  4. Carpenter, K. L., Taylor, S. E., van der Veen, C., Williamson, B. K., Ballantine, J. A. and Mitchinson, M. J. (1995) Lipids and oxidised lipids in human atherosclerotic lesions at different stages of development. Biochim. Biophys. Acta 1256, 141-150. https://doi.org/10.1016/0005-2760(94)00247-V
  5. Chi, H., Barry, S. P., Roth, R. J., Wu, J. J., Jones, E. A., Bennett, A. M. and Flavell, R. A. (2006) Dynamic regulation of pro- and antiinflammatory cytokines by MAPK phosphatase 1 (MKP-1) in innate immune responses. Proc. Natl. Acad. Sci. U.S.A. 103, 2274-2279. https://doi.org/10.1073/pnas.0510965103
  6. Curtiss, L. K., Black, A. S., Bonnet, D. J. and Tobias, P. S. (2012) Atherosclerosis induced by endogenous and exogenous toll-like receptor (TLR)1 or TLR6 agonists. J. Lipid Res. 53, 2126-2132. https://doi.org/10.1194/jlr.M028431
  7. Dje N'Guessan, P., Riediger, F., Vardarova, K., Scharf, S., Eitel, J., Opitz, B., Slevogt, H., Weichert, W., Hocke, A. C., Schmeck, B. et al. (2009) Statins control oxidized LDL-mediated histone modifications and gene expression in cultured human endothelial cells. Arterioscler. Thromb. Vasc. Biol. 29, 380-386. https://doi.org/10.1161/ATVBAHA.108.178319
  8. Erbel, C., Chen, L., Bea, F., Wangler, S., Celik, S., Lasitschka, F., Wang, Y., Bockler, D., Katus, H. A. and Dengler, T. J. (2009) Inhibition of IL-17A attenuates atherosclerotic lesion development in apoE-deficient mice. J. Immunol. 183, 8167-8175. https://doi.org/10.4049/jimmunol.0901126
  9. Erbel, C., Dengler, T. J., Wangler, S., Lasitschka, F., Bea, F., Wambsganss, N., Hakimi, M., Bockler, D., Katus, H. A. and Gleissner, C. A. (2011) Expression of IL-17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability. Basic. Res. Cardiol. 106, 125-134. https://doi.org/10.1007/s00395-010-0135-y
  10. Erridge, C., Webb, D. J. and Spickett, C. M. (2007) 25-Hydroxycholesterol, 7beta-hydroxycholesterol and 7-ketocholesterol upregulate interleukin-8 expression independently of Toll-like receptor 1, 2, 4 or 6 signalling in human macrophages. Free Radic. Res. 41, 260-266. https://doi.org/10.1080/10715760601070091
  11. Garcia-Cruset, S., Carpenter, K. L., Guardiola, F., Stein, B. K. and Mitchinson, M. J. (2001) Oxysterol profiles of normal human arteries, fatty streaks and advanced lesions. Free Radic. Res. 35, 31-41. https://doi.org/10.1080/10715760100300571
  12. Guyton, J. R. and Klemp, K. F. (1994) Development of the atherosclerotic core region. Chemical and ultrastructural analysis of microdissected atherosclerotic lesions from human aorta. Arterioscler. Thromb. 14, 1305-1314. https://doi.org/10.1161/01.ATV.14.8.1305
  13. Hazeki, K., Nigorikawa, K. and Hazeki, O. (2007) Role of phosphoinositide 3-kinase in innate immunity. Biol. Pharm. Bull. 30, 1617-1623. https://doi.org/10.1248/bpb.30.1617
  14. Iwakura, Y. and Ishigame, H. (2006). The IL-23/IL-17 axis in inflammation. J. Clin. Invest. 116, 1218-1222. https://doi.org/10.1172/JCI28508
  15. Kaminska, B. (2005) MAPK signalling pathways as molecular targets for anti-inflammatory therapy--from molecular mechanisms to therapeutic benefits. Biochim. Biophys. Acta 1754, 253-262. https://doi.org/10.1016/j.bbapap.2005.08.017
  16. Kawai, T. and Akira, S. (2006) TLR signaling. Cell Death Differ 13, 816-825. https://doi.org/10.1038/sj.cdd.4401850
  17. Kawai, T. and Akira, S. (2011) Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34, 637-650. https://doi.org/10.1016/j.immuni.2011.05.006
  18. Kim, S. M., Kim, B. Y., Lee, S. A., Eo, S. K., Yun, Y., Kim, C. D. and Kim, K. (2014) 27-Hydroxycholesterol and 7alpha-hydroxycholesterol trigger a sequence of events leading to migration of CCR5- expressing Th1 lymphocytes. Toxicol. Appl. Pharmacol. 274, 462-470. https://doi.org/10.1016/j.taap.2013.12.007
  19. Korn, T., Bettelli, E., Oukka, M. and Kuchroo, V. K. (2009) IL-17 and Th17 Cells. Annu. Rev .Immunol. 27, 485-517. https://doi.org/10.1146/annurev.immunol.021908.132710
  20. Langrish, C. L., Chen, Y., Blumenschein, W. M., Mattson, J., Basham, B., Sedgwick, J. D., McClanahan, T., Kastelein, R. A. and Cua, D. J. (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201, 233-240. https://doi.org/10.1084/jem.20041257
  21. Lemaire-Ewing, S., Prunet, C., Montange, T., Vejux, A., Berthier, A., Bessede, G., Corcos, L., Gambert, P., Neel, D. and Lizard, G. (2005) Comparison of the cytotoxic, pro-oxidant and pro-inflammatory characteristics of different oxysterols. Cell Biol. Toxicol. 21, 97-114. https://doi.org/10.1007/s10565-005-0141-2
  22. Libby, P. (2002) Inflammation in atherosclerosis. Nature 420, 868-874. https://doi.org/10.1038/nature01323
  23. Oppmann, B., Lesley, R., Blom, B., Timans, J. C., Xu, Y., Hunte, B., Vega, F., Yu, N., Wang, J., Singh, K. et al. (2000) Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13, 715-725. https://doi.org/10.1016/S1074-7613(00)00070-4
  24. Pejnovic, N., Vratimos, A., Lee, S. H., Popadic, D., Takeda, K., Akira, S. and Chan, W. L. (2009) Increased atherosclerotic lesions and Th17 in interleukin-18 deficient apolipoprotein E-knockout mice fed high-fat diet. Mol. Immunol. 47, 37-45. https://doi.org/10.1016/j.molimm.2008.12.032
  25. Sandig, H. and Bulfone-Paus, S. (2012) TLR signaling in mast cells: common and unique features. Front. Immunol. 3, 185.
  26. Schroepfer, G. J., Jr. (2000) Oxysterols: modulators of cholesterol metabolism and other processes. Physiol. Rev. 80, 361-554. https://doi.org/10.1152/physrev.2000.80.1.361
  27. Thobe, B. M., Frink, M., Hildebrand, F., Schwacha, M. G., Hubbard, W. J., Choudhry, M. A. and Chaudry, I. H. (2007) The role of MAPK in Kupffer cell toll-like receptor (TLR) 2-, TLR4-, and TLR9-mediated signaling following trauma-hemorrhage. J. Cell. Physiol. 210, 667-675. https://doi.org/10.1002/jcp.20860
  28. Won, K., Kim, S. M., Lee, S. A., Rhim, B. Y., Eo, S. K. and Kim, K. (2012) Multiple signaling molecules are involved in expression of CCL2 and IL-1beta in response to FSL-1, a Toll-like receptor 6 agonist, in macrophages. Korean J. Physiol. Pharmacol. 16, 447-453. https://doi.org/10.4196/kjpp.2012.16.6.447

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