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

Genes & Immunity volume 5, pages 621–630 (2004)Cite this article

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 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.

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Acknowledgements

We truly thank Ms Marta Briarava (Department of Oncological and Surgical Sciences, University of Padova, Italy) for her help with the analysis of microarray data.

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Authors and Affiliations

  1. Department of Oncological and Surgical Sciences, University of Padova, Italy

    S Mocellin, C R Rossi, P Pilati, D Nitti & M Lise

  2. Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA

    M Panelli, E Wang & F M Marincola

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  1. S Mocellin
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Correspondence to S Mocellin.

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Mocellin, S., Panelli, M., Wang, E. et al. IL-10 stimulatory effects on human NK cells explored by gene profile analysis. Genes Immun 5, 621–630 (2004). https://doi.org/10.1038/sj.gene.6364135

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