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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2004-12

AUTHORS

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

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. More... »

PAGES

621

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.gene.6364135

DOI

http://dx.doi.org/10.1038/sj.gene.6364135

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1005442394

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15573087


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