Genes regulated by interferon-gamma in human uterine microvascular endothelial cells.
Interferon (IFN)-gamma plays a critical role in murine uterine spiral artery remodeling for successful pregnancy. The effect of IFN-gamma on human uterine microvasculature, however, remains poorly understood. The aim of this study was to identify the genes regulated by IFN-gamma in human uterine microvascular endothelial cells. The effect of IFN-gamma on the gene expression profile in human uterine microvascular endothelial cells was evaluated by cDNA microarray analysis and quantitative real-time reverse transcriptase-polymerase chain reaction for the selected genes of interest. In vivo expression of the protein encoded by some of these genes in human uterine microvascular endothelial cells was evaluated by Western blotting and immunohistochemistry. Treatment with 10 ng/ml IFN-gamma for 4 h induced a significant > or =2-fold change in 29 genes in pooled human uterine microvascular endothelial cells; a total of 20 genes were up-regulated, whereas nine genes were down-regulated. The genes significantly up-regulated included chemokines (CXCL9, CXCL10, CCL8, IL15RA, and CCL5), enzymes (GBP5, TAP1, CYP27B1, SOD2, MX1, CASP1, and PTGES), and transcription factors (TFAP2C, IRF1, NFE2L3). The genes significantly down-regulated following IFN-gamma treatment included cytokines/cytokine receptors (CSF2, IL1R2, and SPP1), and insulin-like growth factor binding proteins (WISP2 and IGFBP3). The results of the cDNA microarray analysis were confirmed by quantitative real-time reverse transcriptase-polymerase chain reaction for the selected 17 genes of interest. The immunoreactivity for the proteins encoded by IL15RA, IFI30, and MX1 was detected in human uterine microvascular endothelial cells in vivo, whereas the immunoreactivity for CCNA1 and NQO1 was not detectable. These results suggest that IFN-gamma regulates the gene expression involved in natural killer cell recruitment, embryo and trophoblast migration, endometrial decidualization, angiogenesis, angiostasis, and anti-viral infection in human uterine microvascular endothelial cells.
Kitaya
Kotaro
K
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan. kitaya@koto.kpu-m.ac.jp
Yasuo
Tadahiro
T
Yamaguchi
Takeshi
T
Fushiki
Shinji
S
Honjo
Hideo
H
D000328:Adult; D015153:Blotting, Western; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology*; D008875:Middle Aged; D015854:Up-Regulation / Q000187:drug effects; D014599:Uterus / Q000098:blood supply* / Q000166:cytology* / Q000187:drug effects
D007371:Interferon-gamma