Abstract
Interleukin-27 (IL-27) is a novel IL-12 family member that plays a critical role in the regulation of T-cell responses. Its immunoregulatory effects on endothelial cells (EC) remain unexplored. Here we show a role for IL-27 in the induction of major histocompatibility complex (MHC) expression in primary human EC. Stimulation of human umbilical vein ECs by IL-27 rapidly induces IFN regulatory factor-1 and dramatically increases the expression of major histocompatibility class II transactivator (CIITA) isoform IV. Expression of this transactivator correlates with increased MHC class II gene expression. IL-27 also enhances expression of MHC class I molecules. Furthermore expression of beta2-microglobulin and transporter associated with antigen processing-1 transcripts increases in response to IL-27. Additional microarray analysis demonstrates that IL-27 significantly upregulates a panel of genes that correlates with immune regulation, including the chemokines CXCL9, CXCL10, and CX3CL1 in human umbilical vein ECs. This first demonstration that both MHC II and I expression are increased in EC after IL-27 stimulation suggests that IL-27 may be important in conferring immune function on vascular endothelium.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 2
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism
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Cells, Cultured
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Chemokines / genetics
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Chemokines / immunology
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Chemokines / metabolism
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Endothelial Cells / immunology*
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Endothelial Cells / metabolism
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Gene Expression Regulation*
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Genes, MHC Class I
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Genes, MHC Class II
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Histocompatibility Antigens Class II / immunology
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Histocompatibility Antigens Class II / metabolism*
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Humans
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Interferon Regulatory Factor-1 / immunology
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Interferon Regulatory Factor-1 / metabolism*
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Interleukin-17 / immunology
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Interleukin-17 / metabolism*
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Nuclear Proteins / immunology
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Nuclear Proteins / metabolism*
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Oligonucleotide Array Sequence Analysis
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Trans-Activators / immunology
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Trans-Activators / metabolism*
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Umbilical Veins / cytology
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Up-Regulation
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beta 2-Microglobulin / genetics
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beta 2-Microglobulin / immunology
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beta 2-Microglobulin / metabolism
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 2
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ATP-Binding Cassette Transporters
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Chemokines
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Histocompatibility Antigens Class II
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IRF1 protein, human
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Interferon Regulatory Factor-1
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Interleukin-17
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MHC class II transactivator protein
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Nuclear Proteins
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RNA, Messenger
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TAP1 protein, human
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Trans-Activators
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beta 2-Microglobulin