GSK-3β inhibitor modulates TLR2/NF-κB signaling following myocardial ischemia-reperfusion

被引:10
作者
Gao, Hao-Kao [1 ]
Yin, Zhong [1 ]
Zhang, Rong-Qing [1 ]
Zhang, Jun [1 ]
Gao, Feng [2 ]
Wang, Hai-Chang [1 ]
机构
[1] Fourth Mil Med Univ, Dept Cardiol, Xi Jing Hosp, Xian 710032, Peoples R China
[2] Fourth Mil Med Univ, Dept Physiol, Xian 710032, Peoples R China
关键词
Toll like receptor; Ischemia-reperfusion; Innate immunity; TOLL-LIKE RECEPTORS; GLYCOGEN-SYNTHASE KINASE-3; KAPPA-B; GLYCOGEN-SYNTHASE-KINASE-3-BETA; ACTIVATION; INJURY; DYSFUNCTION; EXPRESSION; MICE; TLR2;
D O I
10.1007/s00011-009-0002-1
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The present study defines the expression of Toll-like Receptor 2 (TLR2), and the modulatory role of Glycogen synthase kinase (GSK)-3 beta inhibitor on TLR2/Nuclear Factor-kappa B (NF-kappa B) signaling following myocardial ischemia-reperfusion (MI-R) injury in rats. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were used to analyze the presence and quantity of TLR2 mRNA and protein. Tumor necrosis factor (TNF)-alpha mRNA and interleukin-6 (IL-6) mRNA were analyzed by RT-PCR. The activation of NF-kappa B was detected by Western Blot and the myocardial infarct size by Evans blue-TTC staining. Following 30 min of myocardial ischemia, a significant up-regulation of TLR2 mRNA was revealed by RT-PCR from 1 to 24 h post reperfusion. IHC demonstrated high protein expression levels of TLR2. Administration of the GSK-3 beta inhibitor 4-benzyl-2-methyl-1, 2, 4-thiadiazolidine-3, 5-dione (TDZD-8) 5 min prior to reperfusion following 1 h reperfusion down-regulated mRNA levels of TLR2 and downstream proinflammatory cytokines (P < 0.05 vs. MI-R), decreased the activity of NF-kappa B and the size of the myocardial infarct (P < 0.05 vs. MI-R). Our results demonstrate that TLR2 and its signaling components are activated by MI-R. TDZD-8 administration attenuates TLR2/NF-kappa B signaling, suggesting a possible mechanism whereby GSK-3 beta inhibition improves the outcome of MI-R.
引用
收藏
页码:377 / 383
页数:7
相关论文
共 18 条
[1]   The apoptotic signaling pathway activated by Toll-like receptor-2 [J].
Aliprantis, AO ;
Yang, RB ;
Weiss, DS ;
Godowski, P ;
Zychlinsky, A .
EMBO JOURNAL, 2000, 19 (13) :3325-3336
[2]   Glycogen synthase kinase-3β inhibition attenuates the development of ischaemia/reperfusion injury of the gut [J].
Cuzzocrea, Salvatore ;
Mazzon, Emanuela ;
Esposito, Emanuela ;
Muia, Carmelo ;
Abdelrahman, Maha ;
Di Paola, Rosanna ;
Crisafulli, Concetta ;
Bramanti, Placido ;
Thiemermann, Christoph .
INTENSIVE CARE MEDICINE, 2007, 33 (05) :880-893
[3]   Glycogen synthase kinase-3β regulates NF-κB1/p105 stability [J].
Demarchi, F ;
Bertoli, C ;
Sandy, P ;
Schneider, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (41) :39583-39590
[4]   Glycogen synthase kinase 3β as a target for the therapy of shock and inflammation [J].
Dugo, Laura ;
Collin, Marika ;
Thiemermann, Christoph .
SHOCK, 2007, 27 (02) :113-123
[5]   Toll-like receptors 2-deficient mice are protected against postischemic coronary endothelial dysfunction [J].
Favre, Julie ;
Musette, Philippe ;
Douin-Echinard, Victorine ;
Laude, Karine ;
Henry, Jean-Paul ;
Arnal, Jean-Francois ;
Thuillez, Christian ;
Richard, Vincent .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2007, 27 (05) :1064-1071
[6]   Role of TLR-8 in the activation of nuclear factor κB by oxidative stress in cardiac myocytes [J].
Frantz, S ;
Kelly, RA ;
Bourcier, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (07) :5197-5203
[7]   Role of phosphoinositide 3-kinase in innate immunity [J].
Hazeki, Kaoru ;
Nigorikawa, Kiyomi ;
Hazeki, Osamu .
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2007, 30 (09) :1617-1623
[8]   Requirement for glycogen synthase kinase-3β in cell survival and NF-κB activation [J].
Hoeflich, KP ;
Luo, J ;
Rubie, EA ;
Tsao, MS ;
Jin, O ;
Woodgett, JR .
NATURE, 2000, 406 (6791) :86-90
[9]   Necrotic neuronal cells induce inflammatory Schwann cell activation via TLR2 and TLR3: Implication in Wallerian degeneration [J].
Lee, Hyunkyoung ;
Jo, Eun-Kyeong ;
Choi, Se-Young ;
Oh, Seog Bae ;
Park, Kyungpyo ;
Kim, Joong Soo ;
Lee, Sung Joong .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 350 (03) :742-747
[10]   Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3 [J].
Martin, M ;
Rehani, K ;
Jope, RS ;
Michalek, SM .
NATURE IMMUNOLOGY, 2005, 6 (08) :777-784