Cilostazol prevents retinal ischemic damage partly via inhibition of tumor necrosis factor-alpha-induced nuclear factor-kappa B/activator protein-1 signaling pathway

被引:10
|
作者
Ishizuka, Fumiya [1 ]
Shimazawa, Masamitsu [1 ]
Egashira, Yusuke [1 ,2 ]
Ogishima, Hiromi [1 ]
Nakamura, Shinsuke [1 ]
Tsuruma, Kazuhiro [1 ]
Hara, Hideaki [1 ]
机构
[1] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan
[2] Gifu Univ, Grad Sch Med, Dept Neurosurg, Gifu, Japan
来源
PHARMACOLOGY RESEARCH & PERSPECTIVES | 2013年 / 1卷 / 01期
关键词
Activator protein-1; cilostazol; inflammation; nuclear factor-kappa B; ocular ischemic syndrome; phosphodiesterase III inhibitor; retinal microvascular endothelial cells; tight junction proteins; tumor necrosis factor-alpha;
D O I
10.1002/prp2.6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cilostazol is a specific inhibitor of phosphodiesterase III and is widely used to treat ischemic symptoms of peripheral vascular disease. We evaluated the protective effects of cilostazol in a murine model of ocular ischemic syndrome in which retinal ischemia was induced by 5-h unilateral ligation of both the pterygopalatine artery (PPA) and the external carotid artery (ECA) in anesthetized mice. The effects of cilostazol (30 mg/kg, p. o.) on ischemia/reperfusion (I/R)-induced retinal damage were examined by histological, retinal vascular permeability, and electrophysiological analyses. Using immunoblotting, the protective mechanism for cilostazol was evaluated by examining antiinflammatory effects of cilostazol on the expression of tumor necrosis factors-alpha (TNF-alpha) and tight junction proteins (ZO-1 and claudin-5), and the phosphorylations of nuclear factor-kappa B (NFjB) and c-Jun. The histological analysis revealed that I/R decreased the cell number in the ganglion cell layer (GCL) and the thicknesses of the inner plexiform layer (IPL) and inner nuclear layer (INL), and that cilostazol attenuated these decreases. Additionally, cilostazol prevented the hyperpermeability of blood vessels. Electroretinogram (ERG) measurements revealed that cilostazol prevented the I/R-induced reductions in a-, b-, and oscillatory potential (OP) wave amplitudes seen at 5 days after I/R. Cilostazol inhibited the increased expression of TNF-a and the phosphorylation levels of NF-jB and c-Jun in the retina after I/R. In addition, cilostazol prevented TNF-alpha-induced reduction of ZO-1 and claudin5 expression in human retinal microvascular endothelial cells (HRMECs). These findings indicate that cilostazol may prevent I/R-induced retinal damage partly through inhibition of TNF-a-induced NF-jB/AP-1 signaling pathway.
引用
收藏
页数:12
相关论文
共 50 条
  • [31] Nuclear Factor-Kappa B Family Member RelB Inhibits Human Immunodeficiency Virus-1 Tat-Induced Tumor Necrosis Factor-Alpha Production
    Kiebala, Michelle
    Polesskaya, Oksana
    Yao, Zhenqiang
    Perry, Seth W.
    Maggirwar, Sanjay B.
    PLOS ONE, 2010, 5 (07):
  • [32] Caffeic acid phenethyl ester modulates Helicobacter pylori-induced nuclear factor-kappa B and activator protein-1 expression in gastric epithelial cells
    Abdel-Latif, MMM
    Windle, HJ
    El Homasany, BS
    Sabra, K
    Kelleher, D
    BRITISH JOURNAL OF PHARMACOLOGY, 2005, 146 (08) : 1139 - 1147
  • [33] Prion protein is required for tumor necrosis factor alpha (TNFα)-triggered nuclear factor kappa B (NF-κB) signaling and cytokine production.
    Li, Chaoyang
    FASEB JOURNAL, 2018, 32 (01):
  • [34] Regulation of nuclear factor-κB, activator protein-1, and glutathione levels by tumor necrosis factor-α and dexamethasone in alveolar epithelial cells
    Rahman, I
    BIOCHEMICAL PHARMACOLOGY, 2000, 60 (08) : 1041 - 1049
  • [35] LncRNA-AK149641 regulates the secretion of tumor necrosis factor-α in P815 mast cells by targeting the nuclear factor-kappa B signaling pathway
    Yao Zhou
    Li-na Gu
    Jie Zhang
    Jing Pan
    Jia-min Zhang
    De-yu Zhao
    Feng Liu
    Scientific Reports, 10
  • [36] LncRNA-AK149641 regulates the secretion of tumor necrosis factor-α in P815 mast cells by targeting the nuclear factor-kappa B signaling pathway
    Zhou, Yao
    Gu, Li-na
    Zhang, Jie
    Pan, Jing
    Zhang, Jia-min
    Zhao, De-yu
    Liu, Feng
    SCIENTIFIC REPORTS, 2020, 10 (01)
  • [37] Angiotensin IV activates nuclear transcription factor-kappa B (NF-κB) and activator protein-1 (AP-1) in vascular smooth muscle cells
    Lorenzo, O
    Ruiz-Ortega, M
    Ruperez, M
    Egido, J
    AMERICAN JOURNAL OF HYPERTENSION, 1999, 12 (04) : 178A - 178A
  • [38] Long term environmental tobacco smoke activates nuclear transcription factor-kappa B, activator protein-1, and stress responsive kinases in mouse brain
    Manna, Sunil K.
    Rangasamy, Thirumalai
    Wise, Kimberly
    Sarkar, Shubhashish
    Shishodia, Shishir
    Biswal, Shyam
    Ramesh, Govindarajan T.
    BIOCHEMICAL PHARMACOLOGY, 2006, 71 (11) : 1602 - 1609
  • [39] Hantaan Virus Nucleocapsid Protein Binds to Importin α Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced Activation of Nuclear Factor Kappa B
    Taylor, Shannon L.
    Frias-Staheli, Natalia
    Garcia-Sastre, Adolfo
    Schmaljohn, Connie S.
    JOURNAL OF VIROLOGY, 2009, 83 (03) : 1271 - 1279
  • [40] Shiga toxin type 1 activates tumor necrosis factor-α gene transcription and nuclear translocation of the transcriptional activators nuclear factor-ΚB and activator protein-1
    Sakiri, R
    Ramegowda, B
    Tesh, VL
    BLOOD, 1998, 92 (02) : 558 - 566