TNFα induces inflammatory stress response in microvascular endothelial cells via Akt- and P38 MAP kinase-mediated thrombospondin-1 expression

被引:17
作者
Fairaq, Arwa [1 ,2 ]
Goc, Anna [1 ,2 ]
Artham, Sandeep [1 ,2 ]
Sabbineni, Harika [1 ,2 ]
Somanath, Payaningal R. [1 ,2 ,3 ,4 ]
机构
[1] Univ Georgia, Coll Pharm, Clin & Expt Therapeut, Augusta, GA 30912 USA
[2] Charlie Norwood VA Med Ctr, Augusta, GA 30912 USA
[3] Georgia Regents Univ, Dept Med, Vasc Biol Ctr, Augusta, GA USA
[4] Georgia Regents Univ, Ctr Canc, Augusta, GA USA
基金
美国国家卫生研究院;
关键词
TNF alpha; TSP-1; Inflammation; Endothelium; P38; MAPK; Akt; INHIBITION; PROTEIN; METAANALYSIS; ACTIVATION; RECEPTORS; APOPTOSIS; CYTOKINES; ERK-1/2; SIGNALS;
D O I
10.1007/s11010-015-2440-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Tumor necrosis factor-alpha (TNF alpha) and thrombospondin-1 (TSP-1) are well-known mediators of inflammation. However, a causal relationship between TNF alpha stimuli and TSP-1 expression in endothelial cell stress, and the underlying mechanisms has not yet been investigated. In our study, human microvascular endothelial cells (hMEC) were treated with TNF alpha and analyzed for endothelial dysfunction, TSP-1 expression, and associated mechanisms. TNF alpha treatment induced a dose-dependent increase in TSP-1 expression in hMEC associated with increased endothelial permeability, apoptosis, and reduced proliferation. Whereas TNF alpha activated Akt, ERK, and P38 mitogen-activated protein kinase (P38 MAPK) simultaneously in hMEC, inhibitors of Akt and P38 MAPK, but not ERK blunted TNF alpha-induced TSP-1 expression. Silencing of NF kappa B gene had no significant effect on TNF alpha-induced TSP-1 expression. Our study demonstrates the novel role of TNF alpha in inducing inflammatory stress response in hMEC through Akt- and P38 MAPK-mediated expression of TSP-1, independent of NF kappa B signaling.
引用
收藏
页码:227 / 236
页数:10
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