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Expression of interleukin-15 and its receptor on the surface of stimulated human umbilical vein endothelial cells

Journal of Huazhong University of Science and Technology [Medical Sciences] volume 29, Article number: 527 (2009) Cite this article

Summary

Human interleukin-15 (hIL-15) is an important cytokine to activate endothelial cells and can be regulated by many other cytokines. The aim of this study is to examine the ability of interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) to induce the production of human interleukin-15 (hIL-15) and IL-15 receptor (IL-15Rα) by human umbilical vein endothelial cells (HUVECs). The data are summarized as follows: 1. Northern blot revealed that IL-15 mRNA was up-regulated by IFN-γ and TNF-α. 2. Intracellular IL-15 protein was visualized by fluorescence microscopy, whereas the expression of IL-15 on the surface of HUVECs was detected by fluorescence activated cell sorting (FACS), and no detectable IL-15 in the medium was verified by ELISA. 3. IL-15Rα was detected on the surface of HUVECs by FACS after IFN-γ and TNF-α stimulation, whereas Western blotting revealed that the elevated expression on surface IL-15Rα was not due to the increased protein expression. The conclusion demonstrated from our results is that IFN-γ and TNF-α play an important role in regulating the expression of IL-15 and IL-15Rα on the surface of HUVECs.

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References

  1. Grabstein KH, Eisenman J, Shanebeck K, et al. Cloning of a T cell growth factor that interacts with the β chain of the interleukin-2 receptor. Science, 1994,264(5161):965–968

    PubMed  Article  CAS  Google Scholar 

  2. Burton JD, Bamford RN, Peters C, et al. Lymphokine, provisionally designated interleukin T and produced by a human adult T-cell leukemia line, stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proc Natl Acad Sci USA, 1994,91(11): 4935–4939

    PubMed  Article  CAS  Google Scholar 

  3. Sugamura K, Asao H, Kondo M, et al. The interleukin-2 receptor chain: its role in multiple cytokine receptor complexes and T cell development in XSCID. Annu Rev Immunol, 1996,14:179–205

    PubMed  Article  CAS  Google Scholar 

  4. Giri JG, Kumaki S, Ahdieh M, et al. Identification and cloning of a novel IL-15 binding protein that is structurally related to the α-chain of the IL-2 receptor. EMBO J, 1995,14(15):3654–3663

    PubMed  CAS  Google Scholar 

  5. Minami Y, Kono T, Miyazaki T, et al. The IL-2 receptor complex: its structure, function and target genes. Annu Rev Immunol, 1993,11:245–268

    PubMed  Article  CAS  Google Scholar 

  6. Anderson DM, Kumaki S, Ahdieh M, et al. Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL-15RA and IL-2RA genes. J Biol Chem, 1995,270(50):29 862–29 869

    CAS  Google Scholar 

  7. Wei XQ, Orchardson M, Gracie JA, et al. The Sushi domain of soluble IL-15 receptor alpha is essential for binding IL-15 and inhibiting inflammatory and allogenic responses in vitro and in vivo. J Immunol, 2001,167(1): 277–282

    CAS  Google Scholar 

  8. Fehniger TA, Caligiuri MA. Interleukin 15: biology and relevance to human disease. Blood, 2001,97(1):14–32

    PubMed  Article  CAS  Google Scholar 

  9. Becknell B, Caligiuri MA. Interleukin-2, interleukin-15, and their roles in human natural killer cells. Adv Immunol, 2005,86:209–239

    PubMed  Article  CAS  Google Scholar 

  10. Krishnaswamy G, Kelley J, Yerra L, et al. Human endothelium as a source of multifunctional cytokines: molecular regulation and possible role in human disease. J Interferon Cytokine Res, 1999,19(2):91–104

    PubMed  Article  CAS  Google Scholar 

  11. Angiolillo AL, Kanegane H, Sgadari C, et al. Interleukin-15 promotes angiogenesis in vivo. Biochem Biophys Res Commun, 1997,233(1):231–237

    PubMed  Article  CAS  Google Scholar 

  12. Abdel-Salam BK, Ebaid H. Upregulation of major histocompatibility complex class II, CD83, CD64, and CD14 on polymorphonuclear neutrophils stimulated with interleukin-15. J Microbiol Immunol Infect, 2008,41(6):462–468

    PubMed  CAS  Google Scholar 

  13. Giron-Michel J, Menard F, Negrini S, et al. EBV-associated mononucleosis does not induce long-term global deficit in T-cell responsiveness to IL-15. Blood, 2009, 113(9):4541–4547

    PubMed  Article  CAS  Google Scholar 

  14. Kim HR, Hwang KA, Park SH, et al. IL-7 and IL-15: biology and roles in T-cell immunity in health and disease. Crit Rev Immunol, 2008, 28(4):325–339

    PubMed  Google Scholar 

  15. Liu X, Xiong C, Li C, et al. Modulation of interleukin-15-induced suppression of human neutrophil apoptosis by TNFalpha. J Huazhong Univ Sci Technolog Med Sci, 2007,27(4):354–357

    PubMed  Article  CAS  Google Scholar 

  16. Abbassi O, Kishimoto TK, McIntire LV, et al. E-selectin supports neutrophil rolling in vitro under conditions of flow. J Clin Invest, 1993,92(6):2719–2730

    PubMed  Article  CAS  Google Scholar 

  17. Jones DA, McIntire LV, Smith CW, et al. A two-step adhesion cascade for T cell /endothelial cell interactions under flow conditions. J Clin Invest, 1994,94(6):2443–2450

    PubMed  Article  CAS  Google Scholar 

  18. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem, 1987,162(1):156–159

    PubMed  Article  CAS  Google Scholar 

  19. Burns AR, Bowden RA, Abe Y, et al. P-selectin mediates neutrophil adhesion to endothelial cell borders. J Leukoc Biol. 1999,65(3):299–306

    PubMed  CAS  Google Scholar 

  20. Luettig B, Decker T, Lohmann-Matthes M. Evidence for the existence of two forms of membrane tumor necrosis factor: An integral protein and a molecule attached to its receptor. J Immunol, 1989,143(12):4034–4038

    PubMed  CAS  Google Scholar 

  21. Tagaya Y, Kurys G, Thies TA, et al. Generation of secretable and nonsecretable interleukin 15 isoforms through alternate usage of signal peptides. Proc Natl Acad Sci USA, 1997,94(26): 14 444–14 449

    Article  CAS  Google Scholar 

  22. Musso T, Calosso L, Zucca M, et al. Human monocytes constitutively express membrane-bound, biologically active, and interferon-gamma-upregulated interleukin-15. Blood, 1999,93(10):3531–3539

    PubMed  CAS  Google Scholar 

  23. Gaggero A, Azzarone B, Andrei C, et al. Differential intracellular trafficking, secretion and endosomal localization of two IL-15 isoforms. Eur J Immunol, 1999,29(4): 1265–1274

    PubMed  Article  CAS  Google Scholar 

  24. Chklovskaia E, Nissen C, Landmann L, et al. Cell-surface trafficking and release of flt3 ligand from T lymphocytes is induced by common cytokine receptor gamma-chain signaling and inhibited by cyclosporin A. Blood, 2001,97(4): 1027–1034

    PubMed  Article  CAS  Google Scholar 

  25. Fleming SD, Campbell PA. Macrophages have cell surface IL-10 that regulates macrophage bactericidal activity. J Immunol, 1996,156(3): 1143-

    PubMed  CAS  Google Scholar 

  26. Pereno R, Gaggero A, Scudeletti M, et al. IL-15/IL-15R alpha intracellular trafficking in human cells and protection from apoptosis. Ann N Y Acad Sci, 1999,876:236–245

    PubMed  Article  CAS  Google Scholar 

  27. Bulfone-PauS S, Bulanova E, Pohl T, et al. Death deflected: IL-15 inhibits TNF-alpha-mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL-15Ralpha chain. FASEB J, 1999,13(12): 1575–1585

    PubMed  CAS  Google Scholar 

  28. Waldmann TA, Tagaya Y. The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens. Annu Rev Immunol, 1999,17:19–49

    PubMed  Article  CAS  Google Scholar 

  29. Dubois S, Magrangeas F, Lehours P, et al. Natural splicing of exon 2 of human interleukin-15 receptor alpha-chain mRNA results in a shortened form with a distinct pattern of expression. J Biol Chem, 1999,274(38):26 978–26 984

    Article  CAS  Google Scholar 

  30. Kennedy MK, Park LS. Characterization of interleukin-15 (IL-15) and the IL-15 receptor complex. J Clin Immunol, 1996,16(3):134–143

    PubMed  Article  CAS  Google Scholar 

  31. Pereno R, Giron-Michel J, Gaggero A, et al. IL-15/IL-15Ralpha intracellular trafficking in human melanoma cells and signal transduction through the IL-15Ralpha. Oncogene, 2000, 9(45):5153–5162

    Article  Google Scholar 

  32. Ohteki, T, Suzue K, Maki C, et al. Critical role of IL-15-IL-15R for antigen-presenting cell functions in the innate immune response. Nat Immunol, 2001,2(12):1138–1143

    PubMed  Article  CAS  Google Scholar 

  33. Ozawa A, Tada H, Sugawara Y, et al. Endogenous IL-15 sustains recruitment of IL-2Rbeta and common gamma and IL-2-mediated chemokine production in normal and inflamed human gingival fibroblasts. J Immunol, 2004, 173(8): 5180–5188

    PubMed  CAS  Google Scholar 

  34. Koka R, Burkett P, Chien M, et al. Cutting edge: murine dendritic cells require IL-15R alpha to prime NK cells. J Immunol, 2004,173(6): 3594–3598

    PubMed  CAS  Google Scholar 

  35. Bahary N, Zon Li. Enhanced: endothelium— chicken soup for the endoderm. Science, 2001, 294(5542):530–531

    PubMed  Article  CAS  Google Scholar 

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Author information

Affiliations

  1. College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China

    Xiuping Liu

  2. Hubei Vocational and Technical College, Xiaogan, 432000, China

    Xiuping Liu

  3. Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

    Yumei Zuo

  4. Institute of Organ Transplantation, Key Laboratory of Organ Transplantation, Ministry of Education/Ministry of Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Weina Zhang

  5. College of Agriculture, Northeast Agricultural University, Harbin, 150030, China

    Deguang Yang

  6. Molecular Targets Development Program, National Cancer Institute-Frederick National Institutes of Health Frederick, Frederick, MD, 21702, USA

    Changyun Xiong

  7. Xianggan Medical College Hospital, Huazhong University of Science and Technology, Xiaogan, 432000, China

    Xiaozhou Zhang

Authors
  1. Xiuping Liu
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  2. Yumei Zuo
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  3. Weina Zhang
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  4. Deguang Yang
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  5. Changyun Xiong
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  6. Xiaozhou Zhang
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Additional information

This project was supported by NIH grant HL42550 of USA.

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Liu, X., Zuo, Y., Zhang, W. et al. Expression of interleukin-15 and its receptor on the surface of stimulated human umbilical vein endothelial cells. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 29, 527 (2009). https://doi.org/10.1007/s11596-009-0501-x

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  • DOI: https://doi.org/10.1007/s11596-009-0501-x

Key words

  • endothelial cells
  • interleukin-15
  • interleukin-15 receptor
  • cytokines