Platelet Activating Factor (PAF) Antagonism with Ginkgolide B Protects the Liver Against Acute Injury. Importance of Controlling the Receptor of PAF

Grypioti, A.D.; Kostopanagiotou, Georgia; Demopoulos, Constantinos A.; Roussos, Anastasios; Mykoniatis, Michael G.

doi:10.1007/s10620-007-9982-2

Cited by 20 publications

(19 citation statements)

References 52 publications

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“…In addition, ginkgolide B has many other biological functions. For example, ginkgolide B can specifically inhibit effects of platelet activating factor (PAF) via competitively binding to PAF receptor [25]. In our study, we demonstrated that ginkgolide B effectively inhibited EFV-induced ROS production and endothelial permeability.…”

Section: Discussionmentioning

confidence: 54%

Non-nucleoside reverse transcriptase inhibitor efavirenz increases monolayer permeability of human coronary artery endothelial cells

et al. 2010

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Highly active antiretroviral therapy (HAART) is often associated with endothelial dysfunction and cardiovascular complications. In this study, we determined whether HIV non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) could increase endothelial permeability. Human coronary artery endothelial cells (HCAECs) were treated with EFV (1, 5 and 10 µg/ml) and endothelial permeability was determined by a transwell system with a fluorescence-labeled dextran tracer. HCAECs treated with EFV showed a significant increase of endothelial permeability in a concentration-dependent manner. With real time PCR analysis, EFV significantly reduced the mRNA levels of tight junction proteins claudin-1, occludin, zonula occluden-1 and junctional adhesion molecule-1 compared with controls (P < 0.05). Protein levels of these tight junction molecules were also reduced substantially in the EFV-treated cells by western blot and flow cytometry analyses. In addition, EFV also increased superoxide anion production with dihydroethidium and cellular glutathione assays, while it decreased mitochondrial membrane potential with JC-staining. Antioxidants (ginkgolide B and MnTBAP) effectively blocked EFV-induced endothelial permeability and mitochondrial dysfunction. Furthermore, EFV increased the phosphorylation of MAPK JNK and IκBα, thereby increasing NFκB translocation to the nucleus. Chemical JNK inhibitor and dominant negative mutant JNK and IkBa adenoviruses effectively blocked the effects of EFV on HCAECs. Thus, EFV increases endothelial permeability which may be due to the decrease of tight junction proteins and the increase of superoxide anion. JNK and NFκB activation may be directly involved in the signal transduction pathway of EFV action in HCAECs.

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Section: Discussionmentioning

confidence: 54%

Non-nucleoside reverse transcriptase inhibitor efavirenz increases monolayer permeability of human coronary artery endothelial cells

et al. 2010

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“…; Grypioti et al. ). Ginkgo biloba is a PAF receptor antagonist that is excreted unchanged in the urine (Braquet ; Becker et al.…”

Section: Discussionmentioning

confidence: 97%

Cigarette smoke‐induced urothelial cell damage: potential role of platelet‐activating factor

Kispert

Marentette

Campian

et al. 2017

Physiological Reports

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Cigarette smoking is an environmental risk factor associated with a variety of pathologies including cardiovascular disease, inflammation, and cancer development. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory bladder disease with multiple etiological contributors and risk factors associated with its development, including cigarette smoking. Previously, we determined that cigarette smoking was associated with bladder wall accumulation of platelet activating factor (PAF), a potent inflammatory mediator that facilitates transendothelial cell migration of inflammatory cells from the circulation. PAF has been shown to reduce expression of tight junctional proteins which could ultimately lead to increased urothelial cell permeability. In this study, we observed that cigarette smoke extract (CSE) treatment of human urothelial cells increases PAF production and PAF receptor expression and reduces wound healing ability. After exposure to cigarette smoke for 6 months, wild‐type C57BL/6 mice displayed urothelial thinning and destruction which was not detected in iPLA 2 β −/− (enzyme responsible for PAF production) animals. We also detected increased urinary PAF concentration in IC/BPS patients when compared to controls, with an even greater increase in urinary PAF concentration in smokers with IC/BPS. These data indicate that cigarette smoking is associated with urothelial cell damage that may be a result of increased PAF‐PAF receptor interaction. Inhibition of iPLA 2 β activity or blocking of the PAF‐PAF receptor interaction could serve as a potential therapeutic target for managing cigarette smoke‐induced bladder damage.

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“…; Grypioti et al. ). Extracted from Ginkgo biloba, ginkgolide B is excreted unchanged in the urine making it an ideal therapeutic intervention for managing bladder inflammation (Kimbel ).…”

Section: Discussionmentioning

confidence: 97%

Increased susceptibility to bladder inflammation in smokers: targeting the PAF-PAF receptor interaction to manage inflammatory cell recruitment

2015

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Chronic bladder inflammation can result in a significant reduction in quality of life. Smoking remains a leading preventable risk factor in many diseases. Despite the large amount of evidence supporting the risks of smoking, roughly 45 million people in the United States remain smokers. The impact of cigarette smoking on inflammation is well established, but how smoking promotes bladder inflammation is currently unknown. The aim of this study was to determine if cigarette smoke exposure impacts inflammatory cell adherence to bladder endothelial cells and if targeting the platelet‐activating factor (PAF)–PAF receptor (PAFR) interaction could be beneficial in managing bladder inflammation. In response to cigarette smoke extract (CSE) incubation, bladder endothelial cells from human or mouse displayed increased PAF accumulation, decreased PAF‐AH activity, and increased inflammatory cell adherence. Inhibition of endothelial cell calcium‐independent phospholipase A2 β (iPLA 2 β) with (S)‐BEL, to block PAF production, prevented adherence of inflammatory cells. Pretreatment of inflammatory cells with PAFR antagonists, ginkgolide B or WEB2086 significantly reduced the number of adhered cells to bladder endothelium. Wild‐type mice exposed to cigarette smoke displayed increased presence of inflammatory infiltration which was absent in iPLA 2 β −/− mice and those exposed to room air. In conclusion, cigarette smoke exposure increases endothelial cell PAF accumulation and increased inflammatory cell adherence. Inhibition of PAF accumulation or PAFR antagonism markedly attenuated inflammatory cell adherence to bladder endothelial cells. The results detailed in this study highlight to potential therapeutic targets for managing bladder inflammation.

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Platelet Activating Factor (PAF) Antagonism with Ginkgolide B Protects the Liver Against Acute Injury. Importance of Controlling the Receptor of PAF

Cited by 20 publications

References 52 publications

Non-nucleoside reverse transcriptase inhibitor efavirenz increases monolayer permeability of human coronary artery endothelial cells

Non-nucleoside reverse transcriptase inhibitor efavirenz increases monolayer permeability of human coronary artery endothelial cells

Cigarette smoke‐induced urothelial cell damage: potential role of platelet‐activating factor

Increased susceptibility to bladder inflammation in smokers: targeting the PAF-PAF receptor interaction to manage inflammatory cell recruitment

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