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A synthetic peptide homologous to functional domain of human IL-10 down-regulates expression of MHC class I and transporter associated with antigen processing 1/2 in human melanoma cells

Item Type:Article
Title:A synthetic peptide homologous to functional domain of human IL-10 down-regulates expression of MHC class I and transporter associated with antigen processing 1/2 in human melanoma cells
Creators Name:Kurte, M. and Lopez, M. and Aguirre, A. and Escobar, A. and Aguillon, J.C. and Charo, J. and Larsen, C.G. and Kiessling, R. and Salazar-Onfray, F.
Abstract:Tumor cells treated with IL-10 were shown to have decreased, but peptide-inducible expression of MHC class I, decreased sensitivity to MHC class I-restricted CTL, and increased NK sensitivity. These findings could be explained, at least partially, by a down-regulation of TAP1/TAP2 expression. In this study, IT9302, a nanomeric peptide (AYMTMKIRN), homologous to the C-terminal of the human IL-10 sequence, was demonstrated to mimic these previously described IL-10 effects on MHC class I-related molecules and functions. We observed a dose-dependent down-regulation of MHC class I at the cell surface of melanoma cells after 24-h treatment with IT9302. The EL-10 homologue peptide also caused a dose-dependent inhibition of the IFN-γ-mediated surface induction of MHC class I in a melanoma cell line. We demonstrated, using Western blot and flow cytometry, that IT9302 inhibits the expression of TAP1 and TAP2 proteins, but not MHC class I H chain or low molecular protein molecules. Finally, peptide-treated melanoma cells were shown to be more sensitive to lysis by NK cells in a dose-dependent way. Taken together, these results demonstrate that a small synthetic peptide derived from IL-10 can mimic the Ag presentation-related effects mediated by this cytokine in human melanomas and increase tumor sensitivity to NK cells, which can be relevant in the designing of future strategies for cancer immune therapy.
Keywords:ATP-Binding Cassette Transporters, Cysteine Endopeptidases, Drug Dose-Response Relationship, Eye Neoplasms, Histocompatibility Antigens Class I, Immunologic Cytotoxicity, Interleukin-10, Lymphokine-Activated Killer Cells, Neoplastic Gene Expression Regulation, Melanoma, MHC Class I Genes, Neoplasm Proteins, Oligopeptides, Recombinant Interferon-gamma, Tertiary Protein Structure, Tumor Cell Line
Source:Journal of Immunology
ISSN:0022-1767
Publisher:American Association of Immunologists (U.S.A.)
Volume:173
Number:3
Page Range:1731-1737
Date:1 January 2004
Official Publication:http://www.jimmunol.org/cgi/content/abstract/173/3/1731
PubMed:View item in PubMed

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