IL-10 stimulatory effects on human NK cells explored by gene profile analysis.
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.
Mocellin
S
S
Department of Oncological and Surgical Sciences, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy. mocellins@hotmail.com
Panelli
M
M
Wang
E
E
Rossi
C R
CR
Pilati
P
P
Nitti
D
D
Lise
M
M
Marincola
F M
FM
D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control*; D020411:Oligonucleotide Array Sequence Analysis; D039102:Poly(A)-Binding Proteins; D011506:Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074019:T-Cell Intracellular Antigen-1
D017931:DNA Primers; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D016753:Interleukin-10