Modulation of interleukin-15-induced suppression of human neutrophil apoptosis by TNFα

  • Liu Xiuping  (刘秀平)
  • Xiong Changyun  (熊长云)
  • Li Chunhong  (李春红)
  • Yang Deguang  (杨德光)


Human interleukin-15 (IL-15) is a proinflammatory cytokine to suppress neutrophil apoptosis, which is a potential therapeutic agent. The modulatory effect of TNFα was investigated in IL-15-induced suppression of human neutrophil apoptosis. TNFα was shown to reverse the ability of IL-15 to delay neutrophil apoptosis within certain time course. Moreover, this reverse effect by TNFα might be associated with a reduction of the expression of the anti-apoptotic Bcl-Xl protein detected by Western blotting. It is concluded that TNFα can be used to modulate IL-15-induced suppression of neutrophil apoptosis within certain time course.

Key words

neutrophil interleukin-15 TNFα apoptosis Bcl-Xl 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bamford R N, Grant A J, Burton J D et al. The interleukin (IL)-2 receptor beta chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proc Natl Acad Sci USA, 1994,91:4940–4944PubMedCrossRefGoogle Scholar
  2. 2.
    Grabstein K H, Eisenman J, Shanebeck K et al. Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science,1994, 264:965–968PubMedCrossRefGoogle Scholar
  3. 3.
    Kirman I, Vainer B, Nielsen O H. Interleukin-15 and its role in chronic inflammatory diseases. Inflamm Res, 1998,47:285–289PubMedCrossRefGoogle Scholar
  4. 4.
    Waldmann T, Tagaya Y, Bamford R. Interleukin-2, interleukin-15, and their receptors. Int Rev Immunol, 1998,16:205–226PubMedGoogle Scholar
  5. 5.
    Cassatella M A, McDonald P P. Interleukin-15 and its impact on neutrophil function. Curr Opin Hematol, 2000,7(3):174–177PubMedCrossRefGoogle Scholar
  6. 6.
    Williams N S, Klem J, Puzanov I J et al. Natural killer cell differentiation: insights from knockout and transgenic mouse models and in vitro systems. Immunol Rev, 1998,165:47–61PubMedCrossRefGoogle Scholar
  7. 7.
    Lodolce J, Burkett P, Koka R et al. Interleukin-15 and the regulation of lymphoid homeostasis. Mol Immunol, 2002,39(9):537–544PubMedCrossRefGoogle Scholar
  8. 8.
    Bouchard A, Ratthe C, Girard D. Interleukin-15 delays human neutrophil apoptosis by intracellular events and not via extracellular factors: role of Mcl-1 and decreased activity of caspase-3 and caspase-8. J Leukoc Biol, 2004,75(5):1–8Google Scholar
  9. 9.
    Pelletier M, Ratthe C, Girard D. Mechanisms involved in interleukin-15-induced suppression of human neutrophil apoptosis: role of the anti-apoptotic Mcl-1 protein and several kinases including Janus kinase-2, p38 mitogen-activated protein kinase and extracellular signal-regulated kinases-1/2. FEBS Lett, 2002,532(1–2):164–170PubMedCrossRefGoogle Scholar
  10. 10.
    Elletier M, Lavastre V, Savoie A et al. Modulation of interleukin-15-induced human neutrophil responses by the plant lectrin Viscum album agglutinin-I. Clin Immunol, 2001,101(2):229–236CrossRefGoogle Scholar
  11. 11.
    Ding Z M, Babensee J E, Simon S I et al. Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration. J Immunol, 1999,163(9):5029–5038PubMedGoogle Scholar
  12. 12.
    Walsh G M, Dewson G, Wardlaw A J et al. A comparative study of different methods for the assessment of apoptosis and necrosis in human eosinophils. J Immunol Methods, 1998,217(1-2):153–163PubMedCrossRefGoogle Scholar
  13. 13.
    Laemelli U K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 1970,227:680–685CrossRefGoogle Scholar
  14. 14.
    Girard D, Paquet M E, Paquin R et al. Differential effects of interleukin-15 (IL-15) and IL-2 on human neutrophils: modulation of phagocytosis, cytoskeleton rearrangement, gene expression, and apoptosis by IL-15. Blood, 1996, 88(8):3176–3184PubMedGoogle Scholar
  15. 15.
    Weinmann P, Gaehtgens P, Walzog B. Bcl-Xl-and Bax-alpha-mediated regulation of apoptosis of human neutrophils via caspase-3. Blood, 1999,93(9):3106–3115PubMedGoogle Scholar
  16. 16.
    Oltvai Z N, Milliman C L, Korsmeyer S J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell, 1993, 74(4):609–619PubMedCrossRefGoogle Scholar
  17. 17.
    Sedlak T W, Oltvai Z N, Yang E et al. Multiple Bcl-2 family members demonstrate selective dimerizations with Bax. Proc Natl Acad Sci U S A, 1995,92(17):7834–7838PubMedCrossRefGoogle Scholar
  18. 18.
    Gottschalk A R, Boise L H, Thompson C B et al. Identification of immunosuppressant-induced apoptosis in a murine B-cell line and its prevention by bcl-x but not bcl-2. Proc Natl Acad Sci U S A, 1994,91(15):7350–7354PubMedCrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology 2007

Authors and Affiliations

  • Liu Xiuping  (刘秀平)
    • 1
  • Xiong Changyun  (熊长云)
    • 2
  • Li Chunhong  (李春红)
    • 3
  • Yang Deguang  (杨德光)
    • 4
  1. 1.College of Life Science and TechnologyHuazhong Universty of Science and TechnologyWuhanChina
  2. 2.Molecular Targets Development ProgramNational Cancer Institute-Frederick National Institutes of Health FrederickUSA
  3. 3.Affiliated Tumor HospitalHarbin Medical UniversityHarbinChina
  4. 4.College of AgricultureNortheast Agricultural UniversityHarbinChina

Personalised recommendations