The associated regulators and signal pathway in rIL-16/CD4 mediated growth regulation in Jurkat cells

Cell Res. 2002 Dec;12(5-6):363-72. doi: 10.1038/sj.cr.7290138.

Abstract

IL-16 is a ligand and chemotactic factor for CD4+ T cells. IL-16 inhibits the CD3 mediated lymphocyte activation and proliferation. The effects of IL-16 on the target cells are dependent on the cell type, the presence of co-activators etc. To understand the regulation function and mechanism of IL-16 on target cells, we used a 130 a.a. recombinant IL-16 to study its effects on the growth of Jurkat T leukemia cells in vitro. We found that the rIL-16 stimulated the proliferation of Jurkat cells at low dose (10(-9)M), but inhibited the growth of the cells at higher concentration (10(-5)M). Results showed that 10(-5) M of rIL-16 treatment induced an enhanced apoptosis in Jurkat cells. The treatment blocked the expression of FasL, but up-regulated the c-myc and Bid expression in the cells. Pre-treatment of PKC inhibitor or MEK1 inhibitor markedly increased or decreased the rIL-16 induced growth-inhibiting effects on Jurkat cells, respectively. The results suggested that the rIL-16 might be a regulator for the growth or apoptosis of Jurkat cells at a dose-dependent manner. The growth-inhibiting effects of rIL-16 might be Fas/FasL independent, but, associated with the activation of PKC, up-regulated expression of c-Myc and Bid, and the participation of the ERK signal pathway in Jurkat cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / immunology
  • BH3 Interacting Domain Death Agonist Protein
  • CD4 Antigens / immunology*
  • CD4 Antigens / metabolism
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Carrier Proteins / drug effects
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / immunology
  • Cell Division / drug effects
  • Cell Division / genetics
  • Cell Division / immunology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Fas Ligand Protein
  • Humans
  • Interleukin-16 / genetics
  • Interleukin-16 / immunology*
  • Interleukin-16 / pharmacology
  • Jurkat Cells
  • Leukemia, T-Cell / drug therapy
  • Leukemia, T-Cell / immunology*
  • Leukemia, T-Cell / metabolism
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / immunology
  • Membrane Glycoproteins / drug effects
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Protein Kinase C / drug effects
  • Protein Kinase C / genetics
  • Protein Kinase C / immunology
  • Proto-Oncogene Proteins c-myc / drug effects
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / immunology
  • Recombinant Fusion Proteins / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / immunology*

Substances

  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • CD4 Antigens
  • Carrier Proteins
  • Cell Cycle Proteins
  • Enzyme Inhibitors
  • FASLG protein, human
  • Fas Ligand Protein
  • Interleukin-16
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-myc
  • Recombinant Fusion Proteins
  • Protein Kinase C