KATP channel block inhibits the Toll-like receptor 2-mediated stimulation of NF-κB by suppressing the activation of Akt, mTOR, JNK and p38-MAPK

被引:8
作者
Nam, Yoon Jeong [1 ,2 ]
Kim, Arum [1 ,2 ]
Lee, Min Sung [3 ]
Sohn, Dong Suep [4 ]
Lee, Chung Soo [1 ,2 ]
机构
[1] Chung Ang Univ, Dept Pharmacol, Coll Med, Seoul 156756, South Korea
[2] Chung Ang Univ, Skin Barrier Network Human Resources Dev Team BK2, Seoul 156756, South Korea
[3] SoonChunHyang Univ Hosp, Dept Internal Med, Bucheon 420767, Kyung Gi Do, South Korea
[4] Chung Ang Univ Hosp, Dept Thorac & Cardiovasc Surg, Seoul 156755, South Korea
关键词
Keratinocytes; K-ATP channel blockers; Inflammatory mediator production; Akt; mTOR and NF-kappa B pathways; JNK and p38-MAPK; SENSITIVE POTASSIUM CHANNEL; NORMAL HUMAN KERATINOCYTES; LIPOTEICHOIC ACID; CYTOKINE PRODUCTION; LARGE-CONDUCTANCE; CARDIAC MYOCYTES; OXIDATIVE STRESS; EXPRESSION; CELLS; PATHWAY;
D O I
10.1016/j.ejphar.2017.09.014
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Changes in the K-ATP channel activity have been shown to regulate inflammation and immune responses. Using human keratinocytes, we investigated the effect of K-ATP channel inhibition on inflammatory mediator production in relation to the Toll like receptor-2-mediated-Akt, mTOR and NF-kappa B pathways, as well as JNK and p38MAPK, which regulate the transcription genes involved in immune and inflammatory responses. 5Hydroxydecanoate (a selective K-ATP channel blocker), glibenclamide (a cell surface and mitochondrial K-ATP channel inhibitor), the Akt inhibitor, rapamycin, Bay 11-7085 and N-acetylcysteine reduced the lipoteichoic acid-or peptidoglycan-induced production of cytokines and chemokines, and production of reactive oxygen species and increased the levels and activities of Kir 6.2, NF-kappa B, phosphorylated-Akt and mTOR, and the activation of JNK and p38-MAPK in keratinocytes. Inhibitors of c-JNK (SP600125) and p38-MAPK (SB203580) attenuated the lipoteichoic acid-or peptidoglycan-induced production of inflammatory mediators, the activation of the JNK and p38-MAPK, and the production of reactive oxygen species in keratinocytes. The results show that K-ATP channel blockers may reduce the bacterial component-stimulated production of inflammatory mediators in keratinocytes by suppressing the Toll-like receptor-2-mediated activation of the Akt, mTOR and NF-kappa B pathways, as well as JNK and p38-MAPK. The suppressive effect of K-ATP channel blockers appears to be achieved by the inhibition of reactive oxygen species production.
引用
收藏
页码:190 / 201
页数:12
相关论文
共 55 条
[1]   Curcumin Ameliorates Streptozotocin-Induced Heart Injury in Rats [J].
Abo-Salem, Osama M. ;
Harisa, Gamaleldin I. ;
Ali, Tarek M. ;
El-Sayed, El-Sayed M. ;
Abou-Elnour, Fatma M. .
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, 2014, 28 (06) :263-270
[2]   The role of microorganisms in atopic dermatitis [J].
Baker, BS .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2006, 144 (01) :1-9
[3]  
Begon E, 2007, EUR J DERMATOL, V17, P497
[4]   Cellular reprogramming by gram-positive bacterial components: a review [J].
Buckley, Julliette M. ;
Wang, Jiang Huai ;
Redmond, H. Paul .
JOURNAL OF LEUKOCYTE BIOLOGY, 2006, 80 (04) :731-741
[5]   ATP-sensitive potassium channel: A novel target for protection against UV-induced human skin cell damage [J].
Cao, Cong ;
Healey, Sarah ;
Amaral, Ashley ;
Lee-Couture, Avery ;
Wan, Shu ;
Kouttab, Nicola ;
Chu, Wenming ;
Wan, Yinsheng .
JOURNAL OF CELLULAR PHYSIOLOGY, 2007, 212 (01) :252-263
[6]   Peptidoglycan induces nuclear factor-κB activation and cyclooxygenase-2 expression via Ras, Raf-1, and ERK in RAW 264.7 macrophages [J].
Chen, BC ;
Chang, YS ;
Kang, JC ;
Hsu, MJ ;
Sheu, JR ;
Chen, TL ;
Teng, CM ;
Lin, CH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (20) :20889-20897
[7]   The Antidiabetic Agent Glibenclamide Protects Airway Hyperresponsiveness and Inflammation in Mice [J].
Cui, Wei ;
Zhang, Shufang ;
Cai, Zhijian ;
Hu, Xinlei ;
Zhang, Ruifeng ;
Wang, Yong ;
Li, Na ;
Chen, Zhihua ;
Zhang, Gensheng .
INFLAMMATION, 2015, 38 (02) :835-845
[8]   A Smac-mimetic sensitizes prostate cancer cells to TRAIL-induced apoptosis via modulating both IAPs and NF-kappaB [J].
Dai, Yao ;
Liu, Meilan ;
Tang, Wenhua ;
Li, Yongming ;
Lian, Jiqin ;
Lawrence, Theodore S. ;
Xu, Liang .
BMC CANCER, 2009, 9 :392
[9]   Osteopontin-stimulated apoptosis in cardiac myocytes involves oxidative stress and mitochondrial death pathway: role of a pro-apoptotic protein BIK [J].
Dalal, Suman ;
Zha, Qinqin ;
Singh, Mahipal ;
Singh, Krishna .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2016, 418 (1-2) :1-11
[10]   Lipoteichoic acid from Staphylococcus aureus increases matrix metalloproteinase 9 expression in RAW 264.7 macrophages: Modulation by A2A and A2B adenosine receptors [J].
de Souza, Luiz Fernando ;
Jardim, Fernanda Rafaela ;
Sauter, Ismael Pretto ;
de Souza, Marcela Moreira ;
Barreto, Fabiano ;
Margis, Rogerio ;
Bernard, Elena Aida .
MOLECULAR IMMUNOLOGY, 2009, 46 (05) :937-942