Interleukin-15 improves cytotoxicity of natural killer cells via up-regulating NKG2D and cytotoxic effector molecule expression as well as STAT1 and ERK1/2 phosphorylation

Cytokine. 2008 Apr;42(1):128-36. doi: 10.1016/j.cyto.2008.01.003. Epub 2008 Feb 15.

Abstract

NK cells are crucial components of the innate immune system, providing a first line of defense against infectious pathogens and tumors. IL-15 is the major physiologic growth factor responsible for NK cell differentiation, survival and cytolytic activity of mature NK cells. However, the exact regulatory mechanism of IL-15 on NK cell function is still unclear. In this study, we try to investigate the mechanism of IL-15 on NK cytolysis. Our results demonstrate that IL-15 treatment increased NKG2D transcripts and surface expression in NK cells. NKG2D or MICA blockade attenuated the up-regulation of IL-15 on NK cytolysis, demonstrating that the up-regulatory effect of IL-15 on NK cytolysis is at least partly dependent of the interaction of NKG2D and MICA. Furthermore, IL-15 augmented the expression of cytotoxic effector molecules (TRAIL and Perforin) and the phosphorylation of STAT1 and ERK1/2, which may also contribute the NK lysis. These results may have therapeutic implications when designing cytokine immunotherapy against cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Coculture Techniques
  • Cytotoxicity, Immunologic*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunity, Innate
  • Interferon-gamma / immunology
  • Interleukin-15 / immunology*
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • NK Cell Lectin-Like Receptor Subfamily K
  • Phosphorylation
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Receptors, Natural Killer Cell
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism*

Substances

  • Histocompatibility Antigens Class I
  • Interleukin-15
  • KLRK1 protein, human
  • MHC class I-related chain A
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Interferon-gamma
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3