Effects of prolactin and cortisol on natural killer (NK) cell surface expression and function of human natural cytotoxicity receptors (NKp46, NKp44 and NKp30)

Clin Exp Immunol. 2005 Feb;139(2):287-96. doi: 10.1111/j.1365-2249.2004.02686.x.

Abstract

The surface density of the triggering receptors (e.g. NKp46 and NKp30) responsible for natural killer (NK) cell-mediated cytotoxicity determines the ability of NK cells to kill susceptible target cells. In this study, we show that prolactin up-regulates and cortisol down-regulates the surface expression of NKp46 and NKp30. The prolactin-mediated activation and the cortisol-mediated inhibition of natural cytotoxicity receptor (NCR) surface expression reflects gene regulation at the transcriptional level. NKp46 and NKp30 are the major receptors involved in the NK-mediated killing of K562, a human chronic myelogenous leukaemia cell line. Accordingly, the prolactin dramatically increased the NK-mediated killing of the K562 cell line, whereas cortisol abolished this activity. Our data suggest a mechanism by which prolactin activates the lytic function of NK cells, and cortisol inhibits the NK-mediated attack.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cytotoxicity Tests, Immunologic
  • Flow Cytometry
  • Gene Expression / drug effects
  • Humans
  • Hydrocortisone / pharmacology*
  • Killer Cells, Natural / immunology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Lymphocyte Activation
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Natural Cytotoxicity Triggering Receptor 1
  • Natural Cytotoxicity Triggering Receptor 2
  • Natural Cytotoxicity Triggering Receptor 3
  • Prolactin / pharmacology*
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Statistics, Nonparametric

Substances

  • Membrane Glycoproteins
  • NCR1 protein, human
  • NCR2 protein, human
  • NCR3 protein, human
  • Natural Cytotoxicity Triggering Receptor 1
  • Natural Cytotoxicity Triggering Receptor 2
  • Natural Cytotoxicity Triggering Receptor 3
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic
  • Prolactin
  • Hydrocortisone