Original Research Article
Leptin modulates dose-dependently the metabolic and cytolytic activities of NK-92 cells
Version of Record online: 25 FEB 2013
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 228, Issue 6, pages 1202–1209, June 2013
How to Cite
Lamas, B., Goncalves-Mendes, N., Nachat-Kappes, R., Rossary, A., Caldefie-Chezet, F., Vasson, M.-P. and Farges, M.-C. (2013), Leptin modulates dose-dependently the metabolic and cytolytic activities of NK-92 cells. J. Cell. Physiol., 228: 1202–1209. doi: 10.1002/jcp.24273
- Issue online: 25 FEB 2013
- Version of Record online: 25 FEB 2013
- Accepted manuscript online: 5 NOV 2012 12:21PM EST
- Manuscript Accepted: 19 OCT 2012
- Manuscript Received: 18 MAY 2012
- Doctoral Fellowship (CPER and FEDER 2008)
- Ministère de l'Enseignement Supérieur et de la Recherche. Grant Number: EA4233
Leptin, a hormone-cytokine produced primarily in the adipose tissue, has pleiotropic effects on many biological systems and in several cell types, including immune cells. Hyperleptinemia is associated with immune dysfunction and carcinogenesis. Natural killer (NK) cells are critical mediators of anti-tumor immunity, and leptin receptor deficiency in mice leads to impaired NK function. It was thus decided to explore the in vitro effects of leptin on human NK cell function. NK-92 cells were cultured during 48 h with different leptin concentrations [absence, 10 (physiological), 100 (obesity), or 200 ng/ml (pharmacology)]. Their metabolic activity was assessed using the resazurin test. NK-92 cell cytotoxicity and intracellular IFN-γ production were analyzed by flow cytometry. NK-92 cell mRNA and protein expression levels of cytotoxic effectors were determined by RT-qPCR and Western blot. In our conditions, leptin exerted a dose-dependent stimulatory effect on NK-92 cell metabolic activity. In addition, high leptin concentrations enhanced NK-92 cell cytotoxicity against K562-EGFP and MDA-MB-231-EGFP target cells and inversely reduced cytotoxicity against the MCF-7-EGFP target. At 100 ng/ml, leptin up-regulated both NK cell granzyme B and TRAIL protein expressions and concomitantly down-regulated perforin expression without affecting Fas-L expression. In response to PMA/ionomycin stimulation, the proportion of IFN-γ expressing NK-92 cells increased with 100 and 200 ng/ml of leptin. In conclusion, leptin concentration, at obesity level, variably increased NK-92 cell metabolic activity and modulated NK cell cytotoxicity according to the target cells. The underlying mechanisms are partly due to an up-regulation of TRAIL and IFN-γ expression and a down-regulation of perforin. J. Cell. Physiol. 228: 1202–1209, 2013. © 2012 Wiley Periodicals, Inc.