IL-10 stimulatory effects on human NK cells explored by gene profile analysis.

Published

Journal Article

The molecular mechanisms underlying the increase of natural killer (NK) cell anticancer activity mediated by interleukin (IL)-10 have not been elucidated. The aim of this study was to identify potential molecular mediators of IL-10 stimulatory effects by exploring the NK cell gene display induced by this cytokine. Gene profile was determined by high-throughput cDNA microarray and quantitative real-time PCR. In vitro, NK cells resting or conditioned with IL-10 were tested for cytotoxicity, migration and proliferation. IL-10 enhanced mRNA levels of cell activation/cytotoxicity-related genes (eg secretogranin, TIA-1, HMG-1, interferon-inducible genes) not upregulated by IL-2. In line with these findings, IL-10 increased NK cell in vitro cytotoxicity against Daudi cells. Unlike IL-2, IL-10 did not show any significant effect on NK cell in vitro proliferation and migration. However, gene profile analysis showed that IL-10 increased the expression of cell migration-related genes (eg L-selectin, vascular endothelium growth factor receptor-1, plasminogen activator, tissue; formyl peptide receptor, lipoxin A4 receptor), which might support a stimulatory effect not evident with the in vitro functional assay. Overall, gene profiling allowed us to formulate new hypotheses regarding the molecular pathways underlying the stimulatory effects of IL-10 on NK cells, supporting further investigation aimed at defining its role in cancer immune rejection.

Full Text

Duke Authors

Cited Authors

  • Mocellin, S; Panelli, M; Wang, E; Rossi, CR; Pilati, P; Nitti, D; Lise, M; Marincola, FM

Published Date

  • December 2004

Published In

Volume / Issue

  • 5 / 8

Start / End Page

  • 621 - 630

PubMed ID

  • 15573087

Pubmed Central ID

  • 15573087

International Standard Serial Number (ISSN)

  • 1466-4879

Digital Object Identifier (DOI)

  • 10.1038/sj.gene.6364135

Language

  • eng

Conference Location

  • England