Heme Oxygenase-2 Suppress TNF-α and IL6 Expression via TLR4/MyD88-Dependent Signaling Pathway in Mouse Cerebral Vascular Endothelial Cells

被引：19
作者：
Chen, Ren-Jin [1 ]
Yuan, Hong-Hua [2 ]
Zhang, Teng-Ye [2 ]
Wang, Zhen-Zhen [2 ]
Hu, An-kang [1 ]
Wu, Lian-Lian [2 ]
Yang, Zhang-Ping [3 ]
Mao, Yong-Jiang [3 ]
Ji, De-Jun [3 ]
Zhu, Xiao-Rong [1 ]
机构：
[1] Xuzhou Med Coll, Lab Anim Ctr, Xuzhou 221004, Jiangsu, Peoples R China
[2] Xuzhou Med Coll, Neurobiol Res Ctr, Xuzhou, Jiangsu, Peoples R China
[3] Yangzhou Univ, Anim Sci & Technol Coll, Yangzhou, Jiangsu, Peoples R China
来源：
MOLECULAR NEUROBIOLOGY | 2014年 / 50卷 / 03期
关键词：
Heme oxygenase-2; Tumor necrosis factor alpha; Interleukin-6; CLI-095; Cerebral vascular endothelial cells; TOLL-LIKE RECEPTORS; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; APOPTOSIS; HO-2; INJURY; INFLAMMATION; RECOGNITION; GLUTAMATE; TAK-242;
D O I：
10.1007/s12035-014-8693-x
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Heme oxygenase (HO) represents an intrinsic antiinflammatory system based on its ability to inhibit expression of proinflammatory cytokines. The constitutive isoform heme oxygenase-2 (HO-2) has high expression and activity in cerebral microvascular endothelial cells (CMVEC). This study was undertaken to evaluate the role of HO-2 in regulation of TLR4/MyD88-dependent signaling and to study the effect of HO-2 on the expression and secretion of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and Interleukin-6 (IL6) in CMVEC. HO-2 short hairpin RNA (shRNA) and HO-2 overexpression plasmids were used to observe the effect of HO-2 on proinflammatory cytokines in CMVEC in vitro, and the results showed that the messenger RNA (mRNA) and protein levels of TNF-alpha and IL6 were increased and decreased, respectively, compared with control groups. LPS-stimulated TNF-alpha and IL6 mRNA and protein were also reduced in CMVEC treated with an inhibitor of TLR4 signaling, CLI-095, or HO-2 overexpression. CLI-095 and HO-2 overexpression both reduced TLR4 expression in CMVEC, and HO-2 shRNA blocked these effects of CLI-095. CLI-095 and HO-2 overexpression potently suppressed TLR4/MyD88-dependent proinflammatory cytokine expression in CMVEC. These results suggest that HO-2 plays an important role in protecting CMVEC against cytokine-mediated inflammation.
引用
收藏
页码：971 / 978
页数：8
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