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Reblastatins Inhibit Phenotypic Changes of Monocytes/Macrophages in a Milieu Rich in 27-Hydroxycholesterol

김보영|김민수|이동호|홍영수|최정윤|김관회|손용해
대한면역학회 (The Korean Association of Immunologists)|2020.04|Immune Network|제20권 제2호|pp. 1-18|DOI 10.4110/in.2020.20.e17

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키워드

MonocytesMacrophagesReblastatin27-Hydroxycholesterol

초록

We investigated effects of reblastatins on phenotypic changes in monocytes/macrophages induced by 27-hydroxycholesterol (27OHChol). Treatment of THP-1 monocytic cells with reblastatin derivatives, such as 17-demethoxy-reblastatin (17-DR), 18-dehydroxyl-17-demethoxyreblastatin (WK88-1), 18-hydroxyl-17-demethoxyreblastatin (WK88-2), and 18-hydroxyl-17-demethoxy-4,5-dehydroreblastatin (WK88-3), resulted in blockage of CCL2, CCL3, and CCL4 expression at the transcription and protein levels, which, in turn, impaired migration of monocytes/macrophages and Jurkat T cells expressing CCR5, and almost complete inhibition of transcription of M1 marker cytokines, like CXCL10, CXCL11, and TNF-α. Reblastatins also downregulated surface CD14 as well as soluble CD14 along with inhibition of LPS response and matrix metalloprotease-9 expression. Surface levels of mature dendritic cell (mDC)-specific markers, including CD80, CD83, CD88, CD197, and MHC class I and II molecules, were remarkably down-regulated, and 27OHChol-induced decrease of endocytic activity was recovered following treatment with 17-DR, WK88-1, WK88-2, and WK88-3. However, 15-hydroxyl-17-demethoxyreblastatin (DHQ3) did not affect the molecular or functional changes in monocytic cells induced by 27OHChol. Furthermore, surface levels of CD105, CD137, and CD166 were also down-regulated by 17-DR, WK88-1, WK88-2, and WK88-3, but not by DHQ3. Collectively, results of the current study indicate that, except DHQ3, reblastatins regulate the conversion and differentiation of monocytic cells to an immunostimulatory phenotype and mDCs, respectively, which suggests possible applications of reblastatins for immunomodulation in a milieu rich in oxygenated cholesterol molecules.

Abstract

We investigated effects of reblastatins on phenotypic changes in monocytes/macrophages induced by 27-hydroxycholesterol (27OHChol). Treatment of THP-1 monocytic cells with reblastatin derivatives, such as 17-demethoxy-reblastatin (17-DR), 18-dehydroxyl-17-demethoxyreblastatin (WK88-1), 18-hydroxyl-17-demethoxyreblastatin (WK88-2), and 18-hydroxyl-17-demethoxy-4,5-dehydroreblastatin (WK88-3), resulted in blockage of CCL2, CCL3, and CCL4 expression at the transcription and protein levels, which, in turn, impaired migration of monocytes/macrophages and Jurkat T cells expressing CCR5, and almost complete inhibition of transcription of M1 marker cytokines, like CXCL10, CXCL11, and TNF-α. Reblastatins also downregulated surface CD14 as well as soluble CD14 along with inhibition of LPS response and matrix metalloprotease-9 expression. Surface levels of mature dendritic cell (mDC)-specific markers, including CD80, CD83, CD88, CD197, and MHC class I and II molecules, were remarkably down-regulated, and 27OHChol-induced decrease of endocytic activity was recovered following treatment with 17-DR, WK88-1, WK88-2, and WK88-3. However, 15-hydroxyl-17-demethoxyreblastatin (DHQ3) did not affect the molecular or functional changes in monocytic cells induced by 27OHChol. Furthermore, surface levels of CD105, CD137, and CD166 were also down-regulated by 17-DR, WK88-1, WK88-2, and WK88-3, but not by DHQ3. Collectively, results of the current study indicate that, except DHQ3, reblastatins regulate the conversion and differentiation of monocytic cells to an immunostimulatory phenotype and mDCs, respectively, which suggests possible applications of reblastatins for immunomodulation in a milieu rich in oxygenated cholesterol molecules.

참고문헌 (39)

  1. Madrigal-Matute J, "Heat shock protein 90 inhibitors attenuate inflammatory responses in atherosclerosis", Cardiovasc Res, 86, pp.330~337 (2010)
  2. Mu H, "HSP90 inhibition suppresses inflammatory response and reduces carotid atherosclerotic plaque formation in ApoE mice", Cardiovasc Ther, 35, pp.e12243~ (2017)
  3. Kim J, "The role of heat shock protein 90 in migration and proliferation of vascular smooth muscle cells in the development of atherosclerosis", J Mol Cell Cardiol, 72, pp.157~167 (2014)
  4. Kim W, "Rational biosynthetic engineering for optimization of geldanamycin analogues", ChemBioChem, 10, pp.1243~1251 (2009)
  5. Neckers L, "Heat shock protein 90", Curr Opin Oncol, 15, pp.419~424 (2003)
  6. Zhang Z, "Non-benzoquinone geldanamycin analogs trigger various forms of death in human breast cancer cells", J Exp Clin Cancer Res, 35, pp.149~ (2016)
  7. Qing Zhao, "Anticancer Effects of the Hsp90 Inhibitor 17-Demethoxy-Reblastatin in Human Breast Cancer MDA-MB-231 Cells", Journal of Microbiology and Biotechnology, 24(7), pp.914~920 (2014), 한국미생물·생명공학회[DOI]
  8. Jang WJ, "Anti-tumor activity of WK88-1, a novel geldanamycin derivative, in gefitinib-resistant non-small cell lung cancers with Met amplification", Cancer Sci, 105, pp.1245~1253 (2014)
  9. Martin KO, "7 α-hydroxylation of 27-hydroxycholesterol : biologic role in the regulation of cholesterol synthesis", J Lipid Res, 38, pp.1053~1058 (1997)
  10. DuSell CD, "27-hydroxycholesterol is an endogenous selective estrogen receptor modulator", Mol Endocrinol, 22, pp.65~77 (2008)
  11. DuSell CD, "The endogenous selective estrogen receptor modulator 27-hydroxycholesterol is a negative regulator of bone homeostasis", Endocrinology, 151, pp.3675~3685 (2010)
  12. Umetani M, "27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen", Nat Med, 13, pp.1185~1192 (2007)
  13. Umetani M, "The cholesterol metabolite 27-hydroxycholesterol promotes atherosclerosis via proinflammatory processes mediated by estrogen receptor alpha", Cell Metab, 20, pp.172~182 (2014)
  14. Son Y, "Oxysterols induce transition of monocytic cells to phenotypically mature dendritic cell-like cells", Biochem Biophys Res Commun, 438, pp.161~168 (2013)
  15. Kim SM, "27-Hydroxycholesterol and 7alpha-hydroxycholesterol trigger a sequence of events leading to migration of CCR5-expressing Th1 lymphocytes", Toxicol Appl Pharmacol, 274, pp.462~470 (2014)
  16. Kim SM, "27-Hydroxycholesterol induces recruitment of monocytic cells by enhancing CCL2 production", Biochem Biophys Res Commun, 442, pp.159~164 (2013)
  17. 허윤, "FSL-1, a Toll-like Receptor 2", 6 Agonist, Induces Expression of Interleukin-1α in the Presence of 27-hydroxycholesterol, 2014, pp.18(6), 475~480[DOI]
  18. Kim SM, "27-Hydroxycholesterol up-regulates CD14 and predisposes monocytic cells to superproduction of CCL2 in response to lipopolysaccharide", Biochim Biophys Acta, 1852, pp.442~450 (2015)
  19. Kim W, "Mutasynthesis of geldanamycin by the disruption of a gene producing starter unit : generation of structural diversity at the benzoquinone ring", ChemBioChem, 8, pp.1491~1494 (2007)
  20. Park D, "The adaptor protein Lad associates with the G protein beta subunit and mediates chemokine-dependent T-cell migration", Blood, 109, pp.5122~5128 (2007)
  21. Lee J, "4′-O-Methylalpinumisoflavone inhibits the activation of monocytes", macrophages to an immunostimulatory phenotype induced by 27‑hydroxycholesterol, 2019, pp.43, 2177~2186
  22. Livak KJ, "Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta c(t))method", Methods, 25, pp.402~408 (2001)
  23. Martin TR, "The CD14 differentiation antigen mediates the development of endotoxin responsiveness during differentiation of mononuclear phagocytes", J Leukoc Biol, 56, pp.1~9 (1994)
  24. Senft AP, "Surfactant protein-D regulates soluble CD14 through matrix metalloproteinase-12", J Immunol, 174, pp.4953~4959 (2005)
  25. Son Y, "Dexamethasone suppresses oxysterol-induced differentiation of monocytic cells", Oxid Med Cell Longev, 2016, pp.2915382~ (2016)
  26. Son Y, "Cyclosporin A inhibits differentiation and activation of monocytic cells induced by 27-hydroxycholesterol", Int Immunopharmacol, 69, pp.358~367 (2019)
  27. 손용해, "Diclofenac Inhibits 27-hydroxycholesterol-induced Differentiation of Monocytic Cells into Mature Dendritic Cells", Immune Network, 17(3), pp.179~185 (2017), 대한면역학회[DOI]
  28. Banchereau J, "Immunobiology of dendritic cells", Annu Rev Immunol, 18, pp.767~811 (2000)
  29. Fujimoto Y, "CD83 expression influences CD4+ T cell development in the thymus", Cell, 108, pp.755~767 (2002)
  30. Gavett SH, "Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice", J Exp Med, 182, pp.1527~1536 (1995)
  31. Schober A, "Chemokines in vascular dysfunction and remodeling", Arterioscler Thromb Vasc Biol, 28, pp.1950~1959 (2008)
  32. Liehn EA, "Chemokines : inflammatory mediators of atherosclerosis", Arch Physiol Biochem, 112, pp.229~238 (2006)
  33. Kielian TL, "CD14 and other recognition molecules for lipopolysaccharide : a review", Immunopharmacology, 29, pp.187~205 (1995)
  34. Ostos MA, "Implication of natural killer T cells in atherosclerosis development during a LPS-induced chronic inflammation", FEBS Lett, 519, pp.23~29 (2002)
  35. Waldo SW, "Heterogeneity of human macrophages in culture and in atherosclerotic plaques", Am J Pathol, 172, pp.1112~1126 (2008)
  36. Vinay DS, "Relative abilities of 4-1BB(CD137)and CD28 to co-stimulate the response of cytokine deflected Th1 and Th2 cells", Immunobiology, 200, pp.246~263 (1999)
  37. Li X, "Microvascular endoglin(CD105)expression correlates with tissue markers for atherosclerotic plaque vulnerability in an ageing population with multivessel coronary artery disease", Histopathology, 61, pp.88~97 (2012)
  38. Rauch SJ, "Cholesterol induces apoptosis-associated loss of the activated leukocyte cell adhesion molecule(ALCAM)in human monocytes", Vascul Pharmacol, 54, pp.93~99 (2011)
  39. 손용해, "PI3K and ERK signaling pathways are involved in differentiation of monocytic cells induced by 27-hydroxycholesterol", The Korean Journal of Physiology & Pharmacology, 21(3), pp.301~308 (2017), 대한약리학회

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