Tsai, Yu-ChihYu-ChihTsaiHsieh, Hsyue-JenHsyue-JenHsiehLiao, FangFangLiaoNi, Chih-WenChih-WenNiChao, Yuen-JenYuen-JenChaoHsieh, Chung-YuChung-YuHsiehWang, Danny LingDanny LingWang2008-11-262018-06-282008-11-262018-06-282007http://ntur.lib.ntu.edu.tw//handle/246246/87232Objective: Atherosclerosis is a chronic disease that involves inflammation, in which cytokines, including interferon-gamma (IFNγ), participate. Endothelial cells (ECs) exposed to IFNγ increase the expression of CXC chemokines. ECs subjected to laminar flow (LF) are atheroprotective, despite an unclear mechanism. This study was conducted to analyze whether ECs under LF were protected from IFNγ-induced responses. Methods: IFNγ-treated human umbilical cord ECs were subjected to LF in a well-defined flow chamber system. IFNγ-induced STAT1 activation and downstream target genes were examined. Results: ECs exposed to IFNγ triggered STAT1 activation via the phosphorylation of Tyr701 and Ser727 in STAT1. ECs exposed to LF alone did not activate STAT1. LF exposure of IFNγ-treated ECs significantly attenuated IFNγ-induced Tyr701 phosphorylation in a shear-force- and time-dependent manner, whereas Ser727 phosphorylation was unaffected. Consistently, LF inhibited IFNγ-induced STAT1 binding to DNA. ECs treated with IFNγ induced the expression of three T-cell-specific CXC chemokines (CXCL9, CXCL10 and CXCL11) as well as CIITA, a transcriptional regulator of major histocompatibility complex class II (MHCII). Consistently, LF exposure of IFNγ-treated ECs reduced the expression of CXC chemokines and CIITA. Conclusions: LF attenuates IFNγ-induced responses via the suppression of STAT1 activation. Inhibition by LF of the interferon-induced ECs' response may explain some aspects of LF's atheroprotective effects on the endothelium. ? 2007 European Society of Cardiology.application/pdf634065 bytesapplication/pdfen-USCXC chemokines; Endothelial cells; Interferon-gamma; Laminar flow; STAT1[SDGs]SDG3alpha chemokine; ciita protein; CXCL11 chemokine; CXCL9 chemokine; gamma interferon; gamma interferon inducible protein 10; gene product; interferon; major histocompatibility antigen class 2; serine; STAT1 protein; tyrosine; unclassified drug; article; controlled study; endothelium cell; gene targeting; human; human cell; human tissue; inflammation; laminar flow; nucleotide sequence; priority journal; protein DNA binding; protein expression; protein phosphorylation; shear flow; T lymphocyte; transcription regulation; umbilical cord; Atherosclerosis; Blotting, Western; Cell Movement; Cells, Cultured; Chemokines, CXC; Electrophoretic Mobility Shift Assay; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Humans; Interferon-gamma, Recombinant; Nuclear Proteins; Phosphorylation; Regional Blood Flow; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; STAT1 Transcription Factor; Stress, Mechanical; Time Factors; Trans-Activatorsjournal article10.1016/j.cardiores.2007.02.0302-s2.0-34247892467http://ntur.lib.ntu.edu.tw/bitstream/246246/87232/1/19.pdf