DOI QR코드

DOI QR Code

The Pro-apoptotic Effects of S100A8 and S100A9 in Human Monocytic Leukemia Cells, THP-1

  • Kim, In-Sik (Department of Senior Healthcare, BK21 Plus Program, Graduate School, Eulji University) ;
  • Lee, Ji-Sook (Department of Clinical Laboratory Science, Wonkwang Health Science University)
  • Received : 2018.05.17
  • Accepted : 2018.05.28
  • Published : 2018.06.30

Abstract

S100A8 and S100A9 are involved in pathogenesis of cancer by induction or inhibition of cancer as well as inflammation. In this study, we investigated the association of S100A8 and S100A9 with pathogenesis of leukemia using human monocytic leukemia cells, THP-1. The expression of TLR4, which is a known receptor of S100A8 and S100A9, was examined by using flow cytometry and Western blotting. THP-1 cells have high surface and cytosol expression of TLR4. S100A8 and S100A9 suppressed the cell survival, and this suppression was found to be associated with apoptosis because they increased the number of apoptotic cells in a dose- and a time-dependent manners. However, S100A8 and S100A9 had no effect on the survival and apoptosis of monocytes isolated from the peripheral blood. We next examined the apoptotic effect of lipopolysaccharide (LPS) and monophosphoryl lipid A (MPLA), which are other ligands of TLR4, in THP-1 cells. Lipopolysaccharide had no effect on cell survival, but MPLA is effective on the cell apoptosis. These results suggest that S100A8 and S100A9 may regulate leukemia cell survival via TLR4, which is an essential receptor in the pro-apoptotic mechanism induced by S100A8 and S100A9. These findings may shed light on development of a possible therapeutic drug for leukemia treatment.

Keywords

References

  1. Austermann J, Zenker S, Roth J. S100-alarmins: potential therapeutic targets for arthritis. Expert Opin Ther Targets. 2017. 21: 739-751.
  2. Goyette J, Geczy CL. Inflammation-associated S100 proteins: new mechanisms that regulate function. Amino Acids. 2011. 41: 821-842. https://doi.org/10.1007/s00726-010-0528-0
  3. Kim IS, Gu A, Lee JS. The role of S100A8 and S100A9 in differentiation of human eosinophilic leukemia cells, EoL-1. Biomed Sci Lett. 2017. 23: 44-47. https://doi.org/10.15616/BSL.2017.23.1.44
  4. Kim IS, Lee JS. S100A8 and S100A9 secreted by allergens in monocytes inhibit spontaneous apoptosis of normal and asthmatic neutrophils via the Lyn/akt/ERK pathway. Korean J Clin Lab Sci. 2017. 49: 128-134. https://doi.org/10.15324/kjcls.2017.49.2.128
  5. Laouedj M, Tardif MR, Gil L, Raquil MA, Lachhab A, Pelletier M, Tessier PA, Barabe F. S100A9 induces differentiation of acute myeloid leukemia cells through TLR4. Blood. 2017. 129: 1980-1990. https://doi.org/10.1182/blood-2016-09-738005
  6. Leanderson T, Liberg D, Ivars F. S100A9 as a Pharmacological Target Molecule in Inflammation and Cancer. Endocr Metab Immune Disord Drug Targets. 2015. 15: 97-104. https://doi.org/10.2174/1871530315666150316123854
  7. Lee NR, Park BS, Kim SY, Gu A, Kim DH, Lee JS, Kim IS. Cytokine secreted by S100A9 via TLR4 in monocytes delays neutrophil apoptosis by inhibition of caspase 9/3 pathway. Cytokine. 2016. 86: 53-63. https://doi.org/10.1016/j.cyto.2016.07.005
  8. Lim SY, Yuzhalin AE, Gordon-Weeks AN, Muschel RJ. Tumorinfiltrating monocytes/macrophages promote tumor invasion and migration by upregulating S100A8 and S100A9 expression in cancer cells. Oncogene. 2016. 35: 5735-5745. https://doi.org/10.1038/onc.2016.107
  9. Mao Y, Poschke I, Kiessling R. Tumour-induced immune suppression: role of inflammatory mediators released by myelomonocytic cells. J Intern Med. 2014. 276: 154-170. https://doi.org/10.1111/joim.12229
  10. Maru Y, Tomita T, Deguchi A, Ieguchi K, Takita M, Tsukahara F, Takemura K, Kitao A, Gusovsky F. Drug Targeting Based on a New Concept-Targeting Against TLR4 as an Example. Endocr Metab Immune Disord Drug Targets. 2015. 15: 83-87. https://doi.org/10.2174/187153031502150522123746
  11. Moris D, Spartalis E, Angelou A, Margonis GA, Papalambros A, Petrou A, Athanasiou A, Schizas D, Dimitroulis D, Felekouras E. The value of calprotectin S100A8/A9 complex as a biomarker in colorectal cancer: A systematic review. J BUON. 2016. 21: 859-866.
  12. Nam AR, Kim DH, Kim MJ, Lee JS, Yang SJ, Kim IS. S100A8 induces secretion of MCP-1, IL-6, and IL-8 via TLR4 in Jurkat T cells. Biomed Sci Lett. 2016. 22: 60-64. https://doi.org/10.15616/BSL.2016.22.2.60
  13. Tsai WC, Tsai ST, Jin YT, Wu LW. Cyclooxygenase-2 is involved in S100A2-mediated tumor suppression in squamous cell carcinoma. Mol Cancer Res. 2006. 4: 539-547. https://doi.org/10.1158/1541-7786.MCR-05-0266
  14. Weiguo Cui, Nikhil S. Joshi, Ying Liu, Hailong Meng, Steven H Kleinstein, Susan M. Kaech. TLR4 ligands LPS and MPLA differentially regulate effector and memory CD8+ T cell differentiation J Immunol. 2014. 192: 4221-4232. https://doi.org/10.4049/jimmunol.1302569