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

S. Mocellin, M. Panelli, E. Wang, C. R. Rossi, P. Pilati, D. Nitti, M. Lise, F. M. Marincola

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Abstract

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 stimulatoty 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.

Original languageEnglish
Pages (from-to)621-630
Number of pages10
JournalGenes and Immunity
Volume5
Issue number8
DOIs
Publication statusPublished - Dec 2004
Externally publishedYes

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Keywords

  • Gene profile
  • Human NK cell
  • IL-10

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Mocellin, S., Panelli, M., Wang, E., Rossi, C. R., Pilati, P., Nitti, D., Lise, M., & Marincola, F. M. (2004). IL-10 stimulatory effects on human NK cells explored by gene profile analysis. Genes and Immunity, 5(8), 621-630. https://doi.org/10.1038/sj.gene.6364135