Laminar flow attenuates interferon-induced inflammatory responses in endothelial cells


Tsai YC, Hsieh HJ, Liao F, Ni CW, Chao YJ, Hsieh CY, Wang DL. Laminar flow attenuates interferon-induced inflammatory responses in endothelial cells. Cardiovasc Res 2007;74:497-505.


OBJECTIVE: Atherosclerosis is a chronic disease that involves inflammation, in which cytokines, including interferon-gamma (IFNgamma), participate. Endothelial cells (ECs) exposed to IFNgamma 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 IFNgamma-induced responses. METHODS: IFNgamma-treated human umbilical cord ECs were subjected to LF in a well-defined flow chamber system. IFNgamma-induced STAT1 activation and downstream target genes were examined. RESULTS: ECs exposed to IFNgamma triggered STAT1 activation via the phosphorylation of Tyr701 and Ser727 in STAT1. ECs exposed to LF alone did not activate STAT1. LF exposure of IFNgamma-treated ECs significantly attenuated IFNgamma-induced Tyr701 phosphorylation in a shear-force- and time-dependent manner, whereas Ser727 phosphorylation was unaffected. Consistently, LF inhibited IFNgamma-induced STAT1 binding to DNA. ECs treated with IFNgamma 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 IFNgamma-treated ECs reduced the expression of CXC chemokines and CIITA. CONCLUSIONS: LF attenuates IFNgamma-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.


Tsai, Yu-ChihHsieh, Hsyue-JenLiao, FangNi, Chih-WenChao, Yuen-JenHsieh, Chung-YuWang, Danny LingengResearch Support, Non-U.S. Gov'tNetherlands2007/03/27 09:00Cardiovasc Res. 2007 Jun 1;74(3):497-505. Epub 2007 Mar 2.