Production of IL-10 by melanoma cells: examination of its role in immunosuppression mediated by melanoma.
Previous studies have shown that IL-10 may modulate immune responses towards the humoral arm by inhibiting production of cytokines involved in cell-mediated responses. In the present studies, we found that mRNA to IL-10 could be demonstrated in 66% of melanoma cell lines by PCR amplification of reverse-transcribed mRNA and in supernatants of the cell lines by ELISA. Release into the supernatants increased approximately 2-fold each day up to 3 days. The MW of 35S-labelled IL-10 secreted by melanoma cells was similar to that reported in previous studies. In the present studies we also examined whether IL-10 may be responsible for some of the immunosuppressive effects of the melanoma cell supernatants observed in previous studies, by testing whether MAbs against IL-10 could reverse the inhibitory effects of these supernatants. Recombinant IL-10 and melanoma supernatants were found to inhibit production of TNF-alpha, IFN-gamma, IL-2 and mixed lymphocyte reactions but reversal of these effects of melanoma supernatants by MAbs against IL-10 was only seen in the case of TNF-alpha production. These results extend the range of cell types known to produce IL-10 and indicate that malignancy of certain cell types may lead to unregulated production of IL-10 that could have the potential to modulate immune responses against the tumor.
Chen
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Immunology and Oncology Unit, Mater Misericordiae Hospital, Newcastle, NSW, Australia.
Daniel
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V
Maher
D W
DW
Hersey
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P
D001483:Base Sequence; D015139:Blotting, Southern; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D007376:Interleukin-2 / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008545:Melanoma / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000032:analysis; D012878:Skin Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007376:Interleukin-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10