title: Interleukin-27 upregulates major histocompatibility complex class II expression in primary human endothelial cells through induction of major histocompatibility complex class II transactivator.
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.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Xiao Ming
authors.initials: XM
authors.lastname: Feng
authors.forename: Xiao Li
authors.initials: XL
authors.lastname: Chen
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.forename: Yu Ling
authors.initials: YL
authors.lastname: Zhou
authors.forename: Zhi Bo
authors.initials: ZB
authors.lastname: Han
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhong Chao
authors.initials: ZC
authors.lastname: Han
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000276:immunology / Q000378:metabolism*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000276:immunology / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D018925:Chemokines; D000949:Histocompatibility Antigens Class II; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D020381:Interleukin-17; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; C073119:TAP1 protein, human; D015534:Trans-Activators; D001613:beta 2-Microglobulin