생명과학회지 (Journal of Life Science)

  • 제27권2호
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  • Pages.217-224
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  • 2017
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지
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단핵구세포주 THP-1의 대식세포로의 분화 및 활성화에서 CO의 억제 효과

Carbon Monoxide Inhibits PMA-induced Differentiation in Human Monocytic THP-1 Cells

  • 김다솔 (부산대학교 의과대학 미생물학 및 면역학교실) ;
  • 이미선 (부산대학교 의과대학 미생물학 및 면역학교실) ;
  • 김한솔 (부산대학교 의과대학 의예과) ;
  • 이혜윤 (부산대학교 의과대학 의예과) ;
  • 김오윤 (부산대학교 의과대학 의예과) ;
  • 강예린 (부산대학교 의과대학 의예과) ;
  • 손동현 (부산대학교 의과대학 미생물학 및 면역학교실) ;
  • 김관회 (부산대학교 의과대학 약리학교실) ;
  • 박영철 (부산대학교 의과대학 미생물학 및 면역학교실)
  • Kim, Da Sol (Department of Microbiology & Immunology, Pusan National University College of Medicine) ;
  • Lee, Mi Sun (Department of Microbiology & Immunology, Pusan National University College of Medicine) ;
  • Kim, Han Sol (Department of Premedicine, Pusan National University College of Medicine) ;
  • Lee, Hye Yun (Department of Premedicine, Pusan National University College of Medicine) ;
  • Kim, Oh Yun (Department of Premedicine, Pusan National University College of Medicine) ;
  • Kang, Ye Rin (Department of Premedicine, Pusan National University College of Medicine) ;
  • Sohn, Dong Hyun (Department of Microbiology & Immunology, Pusan National University College of Medicine) ;
  • Kim, Koanhoi (Department of Pharmacology, Pusan National University College of Medicine) ;
  • Park, Young Chul (Department of Microbiology & Immunology, Pusan National University College of Medicine)
  • 투고 : 2016.11.25
  • 심사 : 2017.01.04
  • 발행 : 2017.02.28
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초록

Carbon monoxide (CO)는 세포 보호의 기능을 가지는 항산화 효소인 heme oxygenase-1 (HO-1)의 대사산물로 세포성장, 아폽토시스, 염증에 대한 억제 효과를 보이는 것으로 보고가 이어지고 있고, 이에 관련된 연구가 활발히 진행되고 있는 실정이다. 본 연구에서는 CO가 단핵구의 대식세포로의 분화 및 그 활성화 과정에 미치는 영향을 인간 단핵구세포주 THP-1을 이용하여 조사하였다. CO-releasing compound인 CORM-2는 phorbol 12-myristate 13-acetate (PMA)로 자극한 THP-1 세포에서 viability와 증식에는 큰 영향을 주지 않았으나 부착능의 뚜렷한 감소를 보였다. 그리고, CORM-2는 대식세포의 막표면 분화 인자인 CD14, CD11b 및 CD18의 발현과 latex beads를 이용한 포식 기능을 현저히 억제하였다. 다음으로, 배양중인 THP-1 세포를 PMA로 6일 동안 대식세포로 분화시킨 후 inflammatory cytokines의 분비와 포식 기능을 조사하였다. CORM-2의 처리는 lipopolysaccaride (LPS)로 자극한 대식세포로부터 분비되는 IL-6와 $TNF-{\alpha}$의 분비를 감소시켰다. 또한, 분화된 대식세포에 E. coli (K-12 strain) bioparticles를 이용하여 포식 기능을 측정한 결과 CORM-2를 처리한 세포에서는 현저히 감소되는 경향을 보였다. 이를 종합해 볼 때, CO는 항원 인식과 포식 기능에 관여하는 막단백질의 발현을 저해함으로써 단핵구의 분화과정을 억제하였고, 분화된 대식세포의 inflammatory cytokines의 분비 및 포식 기능을 저해함으로써 활성화 과정도 억제하는 것으로 보인다.

Carbon monoxide (CO), a reaction product of cytoprotective enzyme heme oxygenase-1 (HO-1), is a gaseous messenger with anti-proliferative, anti-apoptotic, and anti-inflammatory actions in many cell types. Here, we investigated the role of CO on the process of monocyte differentiation induced by phorbol 12-myristate 13-acetate (PMA) in human monocytic THP-1 cells. CORM-2 (tricarbonyldichlororuthenium (II) dimer, $Ru2Cl_4(CO)_6$), a CO-releasing compound, decreased a marked cell adherence with a slight reduction of proliferation in monocytic THP-1 cells treated with PMA. And, CORM-2 significantly inhibited expression of differentiation markers such as CD14, CD11b plus CD18 (macrophage-1 antigen, Mac-1 or complement receptor 3, CR3) and phagocytosis of carboxylate-modified red fluorescent latex beads, in PMA-stimulated THP-1 cells. For the further experiments, differentiation of PMA-treated cells was enhanced after the initial 2 days stimulus by removing the PMA-containing media then incubating the cells in fresh media for a another 4 days. And, we observed the secretion of inflammatory cytokines and phagocytosis in differentiated macrophages. Treatment with CORM-2 significantly abolished the secretion of IL-6, $TNF-{\alpha}$ and phagocytosis using fluorescence-conjugated E. coli (K-12 strain) bioparticles in lipopolysaccharide (LPS)-stimulated differentiated macrophages. In conclusion, these results suggest that CO inhibits the differentiation of monocytic THP-1 cells as well as the activation of differentiated macrophages.

키워드

참고문헌

  1. Carroll, M. C. 1998. The role of complement and complement receptors in induction and regulation of immunity. Annu. Rev. Immunol. 16, 545-568. https://doi.org/10.1146/annurev.immunol.16.1.545
  2. Chen, Q. and Catharine, R. A. 2004. Retinoic acid regulates cell cycle progression and cell differentiation in human monocytic THP-1 cells. Exp. Cell Res. 297, 68-81. https://doi.org/10.1016/j.yexcr.2004.02.017
  3. Dupuy, A. G. and Caron, E. 2008. Integrin-dependent phagocytosis: spreading from microadhesion to new concepts. J. Cell Sci. 121, 1773-1783. https://doi.org/10.1242/jcs.018036
  4. Erdei, A., Kohler, V., Schafer, H. and Burger, R. 1992. Macrophage-bound C3 fragments as adhesion molecules modulate presentation of exogenous antigens. Immunobiology 185, 314-326. https://doi.org/10.1016/S0171-2985(11)80649-2
  5. Freitas, A., Alves-Filho, J. C., Secco, D. D., Neto, A. F., Ferreira, S. H., Barja-Fidalgo, C. and Cunha, F. Q. 2006. Heme oxygenase/carbon monoxide-biliverdin pathway down regulates neutrophil rolling, adhesion and migration in acute inflammation. Br. J. Pharmacol. 149, 345-354. https://doi.org/10.1038/sj.bjp.0706882
  6. Keyse, S. M. and Tyrrell, R. M. 1989. Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblast by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc. Natl. Acad. Sci. USA 86, 99-103. https://doi.org/10.1073/pnas.86.1.99
  7. Kim, H. P., Ryter, S. W. and Choi, A. M. 2006. CO as a cellular signaling molecule. Annu. Rev. Pharmacol. Toxicol. 46, 411-449. https://doi.org/10.1146/annurev.pharmtox.46.120604.141053
  8. Kim, H. S., Loughran, P. A., Rao, J., Billiar, T. R. and Zuckerbraun, B. S. 2008. Carbon monoxide activates NF-kappaB via ROS generation and Akt pathways to protect against cell death of hepatocytes. Am. J. Physiol. Gastrointest. Liver Physiol. 295, G146-152. https://doi.org/10.1152/ajpgi.00105.2007
  9. Kirkby, K. A. and Adin, C. A. 2006. Products of heme oxygenase and their potential therapeutic applications. Am. J. Physiol. Renal Physiol. 290, F563-571. https://doi.org/10.1152/ajprenal.00220.2005
  10. Kitchens, R. L. 2000. Role of CD14 in cellular recognition of bacterial lipopolysaccharides. Chem. Immunol. 74, 61-82.
  11. Lee, P. J., Jiang, B. H., Chin, B. Y., Iyer, N. V., Alam, J., Semenza, G. L. and Choi, A. M. 1997. Hypoxia-inducible factot-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxia. J. Biol. Chem. 272, 5375-5381. https://doi.org/10.1074/jbc.272.9.5375
  12. Linton, M. F. and Fazio, S. 2001. Class A scavenger receptors, macrophages, and atherosclerosis. Curr. Opin. Lipidol. 12, 489-495. https://doi.org/10.1097/00041433-200110000-00003
  13. Maines, M. D. 1988. Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J. 2, 2557-2568. https://doi.org/10.1096/fasebj.2.10.3290025
  14. Mazzola, S., Forni, M., Albertini, M., Bacci, M. L., Zannoni, A., Gentilini, F., Lavitrano, M., Bach, F. H., Otterbein, L. E. and Clement, M. G. 2005. Carbon monoxide pretreatment prevents respiratory derangement and ameliorates hyperacute endotoxic shock in pigs. FASEB J. 19, 2045-2047. https://doi.org/10.1096/fj.05-3782fje
  15. McCarthy, D. M., San Miguel, J., Freake, H. C., Green, P. M., Zola, H., Catowsky, D. and Goldman, J. 1983. 1,25-dihydroxyvitamin $D_3$ inhibits proliferation of human promyelocytic leukemia (HL-60) cells and induces monocyte-macrophage differentiation in HL-60 and normal human bone marrow cells. Leuk. Res. 7, 51-55. https://doi.org/10.1016/0145-2126(83)90057-7
  16. Motterlini, R., Mann, B. E. and Foresti, R. 2005. Therapeutic applications of carbon monoxide-releasing molecules. Expert Opin. Investig. Drugs 14, 1305-1318. https://doi.org/10.1517/13543784.14.11.1305
  17. Muraosa, Y. and Shibahara, S. 1993. Identification of a cisregulatory element and putative trans-acting factors responsible for 12-O tetradecanoylphorbol 13-acetate (TPA)-mediated induction of heme oxygenase expression in myelomonocytic cell lines. Mol. Cell. Biol. 13, 7881-7891. https://doi.org/10.1128/MCB.13.12.7881
  18. Naidu, S., Wijayanti, N., Santoso, S., Kietzmann, T. and Immenschuh, S. 2008. An atypical NF-kB-regulated pathway mediates phorbol ester-dependent heme oxygenase-1 gene activation in monocytes. J. Immunol. 181, 4113-4123. https://doi.org/10.4049/jimmunol.181.6.4113
  19. Nakahira, K., Kim, H. P., Geng, X. H., Nakao, A., Wang, X., Murase, N., Drain, P. F., Wang, X., Sasidhar, M., Nabel, E. G., Takahashi, T., Lukacs, N. W., Morita, K. and Choi, A. M. 2006. Carbon monoxide differentially inhibits TLR signaling pathways by regulating ROS induced trafficking of TLRs to lipid rafts. J. Exp. Med. 203, 2377-2389. https://doi.org/10.1084/jem.20060845
  20. Oliva, C. R., Swiecki, M. K., Griguer, C. E., Lisanby, M. W., Bullard, D. C., Turnbough Jr, C. L. and Kearney, J. F. 2008. The integrin Mac-1 (CR3) mediates internalization and directs Bacillus anthracis spores into professional phagocytes. Proc. Natl. Acad. Sci. USA 105, 1261-1266. https://doi.org/10.1073/pnas.0709321105
  21. Otterbein, L. E., Bach, F. H., Alam, J., Soares, M., Lu, T. H, Wysk, M., Davis, R. J., Flavell, R. A. and Choi, A. M. 2000. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat. Med. 6, 422-428. https://doi.org/10.1038/74680
  22. Pae, H. O., Choi, B. M., Oh, G. S., Lee, M. S., Ryu, D. G., Rhew, H. Y., Kim, Y. M. and Chung, H. T. 2004. Roles of heme oxygenase-1 in the antiproliferative and antiapoptotic effects of nitric oxide on Jurkat T cells. Mol. Pharmacol. 66, 122-128. https://doi.org/10.1124/mol.66.1.122
  23. Pae, H. O., Oh, G. S., Choi, B. M., Chae, S. C., Kim, Y. M., Chung, K. R. and Chung, H. T. 2004. Carbon monoxide produced by heme oxygenase-1 suppresses T cell proliferation via inhibition of IL-2 production. J. Immunol. 172, 4744-4751. https://doi.org/10.4049/jimmunol.172.8.4744
  24. Ranoa, D. R., Kelley, S. L. and Tapping, R. I. 2013. Human lipopolysaccharide-binding protein (LBP) and CD14 independently deliver triacylated lipoproteins to Toll-like receptor 1 (TLR1) and TLR2 and enhance formation of the ternary signaling complex. J. Biol. Chem. 288, 9729-9741. https://doi.org/10.1074/jbc.M113.453266
  25. Rosen, H. and Law, S. K. 1990. The leukocyte cell surface receptor(s) for the iC3b product of complement. Curr. Top. Microbiol. Immunol. 153, 99-122.
  26. Ryter, S. W., Alam, J. and Choi, A. M. 2006. Heme oxygenase-1/carbon monoxide: From basic science to therapeutic applications. Physiol. Rev. 86, 583-650. https://doi.org/10.1152/physrev.00011.2005
  27. Ryter, S. W. and Otterbein, L. E. 2004. Carbon monoxide in biology and medicine. Bioessays 26, 270-280. https://doi.org/10.1002/bies.20005
  28. Sakamoto, H., Aikawa, M., Hill, C. C., Weiss, D., Taylor, W. R., Libby, P. and Lee, R. T. 2001. Biochemical strain induces class a scavenger receptor expression in human monocyte/macrophages and THP-1 cells: a potential mechanism of increased atherosclerosis in hypertension. Circulation 104, 109-114. https://doi.org/10.1161/hc2701.091070
  29. Sarady, J. K., Zuckerbraun, B. S., Bilban, M., Wagner, O., Usheva, A., Liu, F., Ifedigbo, E., Zamora, R., Choi, A. M. and Otterbein, L. E. 2004. Carbon monoxide protection against endotoxic shock involves reciprocal effects on iNOS in the lung and liver. FASEB J. 18, 854-856. https://doi.org/10.1096/fj.03-0643fje
  30. Seo, G. S., Lee, S. H., Choi, S. C., Choi, E. Y., Oh, H. M., Choi, E. J., Park, D. S., Kim, S. W., Kim, T. H., Nah, Y. H., Kim, S., Kim, S. H., Yoo, S. H. and Jun, C. D. 2006. Iron chelator induces THP-1 cell differentiation potentially by modulating intracellular glutathione levels. Free Radic. Biol. Med. 40, 1502-1512. https://doi.org/10.1016/j.freeradbiomed.2005.12.020
  31. Shan, Y., Lambrecht, R. W., Donohue, S. E. and Bonkovsky, H. L. 2006. Role of Bach1 and Nrf2 in up-regulation of the heme oxygenase-1 gene by cobalt protoporphyrin. FASEB J. 20, 2651-2653. https://doi.org/10.1096/fj.06-6346fje
  32. Song, J. D., Lee, S. K., Park, S. E., Kim, K. M., Kim, K., Park, Y. M. and Park, Y. C. 2011. Cobalt protoporphyrin induces differentiation of monocytic THP-1 cells through regulation of cytoplasmic Ref-1-related NADPH oxidase activity. Int. J. Mol. Med. 28, 841-845.
  33. Song, R., Mahidhara, R. S., Zhou, Z., Hoffman, R. A., Seol, D. W., Flavell, R. A., Billiar, T. R., Otterbein, L. E. and Choi, A. M. 2004. Carbon monoxide inhibits T lymphocyte proliferation via caspase-dependent pathway. J. Immunol. 172, 1220-1226. https://doi.org/10.4049/jimmunol.172.2.1220
  34. Srisook, K., Han, S. S., Choi, H. S., Li, M. H., Ueda, H., Kim, C. and Cha, Y. N. 2006. CO from enhanced HO activity or from CORM-2 inhibits both O2- and NO production and downregulates HO-1 expression in LPS-stimulated macrophages. Biochem. Pharmacol. 71, 307-318. https://doi.org/10.1016/j.bcp.2005.10.042
  35. Taketani, S., Kohno, H., Yoshinaga, T. and Tokunaga, R. 1989. The human 32-kDa stress protein induced by exposure to arsenite and cadmium ions is heme oxygenase. FEBS Lett. 245, 173-176. https://doi.org/10.1016/0014-5793(89)80215-7
  36. Tenhunen, R., Marver, H. S. and Schmid, R. 1968. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc. Natl. Acad. Sci. USA 61, 748-755. https://doi.org/10.1073/pnas.61.2.748
  37. Tsuchiya, S., Kobayashi, Y., Goto, Y., Okumura, H., Nakae, S., Konno, T. and Tada, K. 1982. Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester. Cancer Res. 42, 1530-1536.
  38. Ueki, K., Tabeta, K., Yoshie, H. and Yamazaki, K. 2002. Self-heat shock protein 60 induces tumor necrosis factor-alpha in monocyte-derived macrophages: possible role in chronic inflammatory peritoneal disease. Clin. Exp. Immunol. 127, 72-77. https://doi.org/10.1046/j.1365-2249.2002.01723.x
  39. van Spriel, A. B., van Ojik, H. H., Bakker, A., Jansen, M. J. and van de Winkel, J. G. 2003. Mac-1 (CD11b/CD18) is crucial for effective Fc receptor-mediated immunity to melanoma. Blood 101, 253-258. https://doi.org/10.1182/blood.V101.1.253
  40. Vignali, D. A., Bickle, Q. D., Crocker, P. and Taylor, M. G. 1990. Antibody-dependent killing of Schistosoma mansoni schistosomula in vitro by starch-elicited murine macrophages. Critical role of the cell surface integrin Mac-1 in killing mediated by the anti-Mr 16,000 mAb B3A. J. Immunol. 144, 4030-4037.
  41. Wagner, C. T., Durante, W., Christodoulides, N., Hellums, J. D. and Schafer, A. I. 1997. Hemodynamic forces induce the expression of heme oxygenase in cultured vascular smooth muscle cells. J. Clin. Invest. 100, 589-596. https://doi.org/10.1172/JCI119569
  42. Yu, R., Chen, C., Mo, Y. Y., Hebbar, V., Owuor, E. D., Tan, T. H. and Kong, A. N. 2000. Activation of mitogen-activated protein kinase pathways induces antioxidant response element-mediated gene expression via a Nrf2-dependent mechanism. J. Biol. Chem. 275, 39907-39913. https://doi.org/10.1074/jbc.M004037200