Interleukin 10 decreases MICA expression on melanoma cell surface.

Abstract

Natural-killer group 2, member D (NKG2D) binds to a variety of ligands, including the major histocompatibility complex (MHC) class I chain-related proteins (MIC) and UL16-binding proteins (ULBP). It is regarded as a co-activating receptor on NK cells, having an important role in the cell-mediated immune response to tumours. We studied the influence of interleukin (IL)-10 on the regulation of MIC and ULBP expression on melanoma cells, and its effect on the cytotoxic function of NK cells in vitro. Here, we show that, in the presence of IL-10, FMS mel and BL mel cell lines decreased MICA and ULBP2 surface expression, whereas MHC class I did not change substantially on the cell surface. MICA mRNA levels decreased in IL-10-treated FMS and IL-10-transduced BL cell lines. Interestingly, we observed that MICB surface expression and its mRNA levels increased upon IL-10 treatment in a melanoma cell line. These changes in NKG2D ligands surface expression patterns owing to IL-10 treatment resulted in an effect on lysis susceptibility mediated by lymphocyte-activated killer cells, as tumour cell lines that displayed a higher decrease of MICA on their surface had lower levels of lysis. In addition, expression of CD107a was downregulated on the surface of NK cells following stimulation with IL-10-treated FMS cells. Our results suggest a novel function for IL-10 in the modulation of NKG2D ligand expression and in the control of cytotoxicity mediated by NKG2D/NKG2D ligand axis.

• Authors: Antonio E Serrano, Evelyn Menares-Castillo, Macarena Garrido-Tapia, Carolina Hager Ribeiro, Carolina J Hernández, Ariadna Mendoza-Naranjo, Marcela Gatica-Andrades, Rodrigo Valenzuela-Diaz, Roberto Zúñiga, Mercedes N López, Flavio Salazar-Onfray, Juan-Carlos Aguillón, María-Carmen Molina
• Journal: Immunology and cell biology (Immunol Cell Biol) Vol. 89 Issue 3 Pg. 447-57 (Mar 2011) ISSN: 1440-1711 [Electronic] United States
• PMID: 20714339 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Histocompatibility Antigens Class I
• KLRK1 protein, human
• Ligands
• MHC class I-related chain A
• NK Cell Lectin-Like Receptor Subfamily K
• Receptors, Interleukin-10
• Interleukin-10

Topics

• Cell Line, Tumor
• Cytotoxicity, Immunologic (drug effects)
• Down-Regulation
• Gene Expression Regulation, Neoplastic (drug effects)
• Histocompatibility Antigens Class I (metabolism)
• Humans
• Interleukin-10 (immunology, pharmacology)
• K562 Cells
• Killer Cells, Natural (immunology, metabolism)
• Ligands
• Lymphocyte Activation (drug effects, immunology)
• Melanoma (metabolism)
• NK Cell Lectin-Like Receptor Subfamily K (immunology, metabolism)
• Receptors, Interleukin-10 (antagonists & inhibitors)