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Roles of BN52021 in platelet-activating factor pathway in inflammatory MS1 cells

World Journal of Gastroenterology 2013年第25期19卷 3969-3979页

作者： Shi-Hai Xia Xiao-Hui Xiang Kai Chen Wei Xu Department of Hepatopancreatobiliary and Splenic Medicine Affiliated Hospital of the Logistics University of the Chinese People's Armed Police Force

AIM: To determine the effects of BN52021 on platelet-activating factor receptor (PAFR) signaling molecules under lipopolysaccharide (LPS)-induced inflammatory conditions in MS1 cells. METHODS: MS1 cells (a mouse pancreatic islet endothelial cell line) were grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, 2 mmol/L glutamine and 100 μg/mL penicillin/streptomycin in 5% CO 2 at 37 ℃. After growth to confluency in media, the cells were processed for subsequent studies. The MS1 cells received 0, 0.1, 1 and 10 μg/mL LPS in this experiment. The viability/prolifera-tion of the cells induced by LPS was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Apoptosis and necrosis of the cells under the inflammatory condition described previously were observed using Hoechst 33342-propidium iodide staining. Adenylate cyclase (AC), phospholipase A 2 (PLA 2 ), phospholipase Cβ (PLCβ), protein tyrosine kinase (PTK), G protein-coupled receptor kinases (GRK) and p38-mitogen-activated protein kinase (p38 MAPK) mRNA in the PAFR signaling pathway were measured by real-time polymerase chain reaction. The protein expression level of phosphorylated AC (p-AC), phosphorylated PLA 2 (p-PLA 2 ), phosphorylated PTK (p-PTK), phosphorylated p38 MAPK (p-p38 MAPK), PLCβ and GRK was measured using Western blotting analysis. RESULTS: The activity of MS1 cells incubated with dif- ferent concentrations of LPS for 6 h decreased significantly in the 1 μg/mL LPS group (0.49 ± 0.10 vs 0.67 ± 0.13, P < 0.05) and 10 μg/mL LPS group (0.44 ± 0.10 vs 0.67 ± 0.13, P < 0.001), but not in 0.1 μg/mL group. When the incubation time was extended to 12 h (0.33 ± 0.05, 0.32 ± 0.03 and 0.25 ± 0.03 vs 0.69 ± 0.01) and 24 h (0.31 ± 0.01, 0.29 ± 0.03 and 0.25 ± 0.01 vs 0.63 ± 0.01), MS1 cell activity decreased in all LPS concentration groups compared with the blank control (P < 0.001). BN52021 significantly improved the cell activity when its c

关键词： BN52021 platelet-activating factor receptor Signaling pathway Inflammation Pancreatitis

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platelet-activating factor mediates hydrogen peroxide induced endothelial-leukocyte adhesion

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Journal of Medical Colleges of PLA(China) 1992年第3期7卷 236-241页

作者：丁自强李少华吴中立 Department of Pathophysiology Second Military Medical UniversityShanghai 200433

The effects of hydrogen peroxide（H2O2）on endothelial-polymorphonuclear leuko-cyte（EC-PMN）adhesion and their mechanisms were studied in cultured bovine pulmonaryartery endothelial monolayers in vitro.H2O2 at various concentrations(10-3,10-2,10-1mol/Lrespectively)stimulated EC-dependent PMN adhesion,of which 10-2mol/L H2O2 was the mostpotent one,increasing adhesion to 2.3 times that of the *** of PMNs with SRI63-441,a platelet-activating factor（PAF）receptor antagonist,had no inhibition effect on H2O2induced EC-PMN *** of ECs with SRI 63-441 before H2O2 exposure signifi-cantly decreased PMN adherence to *** of ECs with phospholipase A2 inhibitorp-bromophenacyl-bromide or calmodulin antagonist chlorpromazine and calcium ion chelate EG-TA obviously decreased H2O2 induced increment of EC-PMN *** results suggestthat H2O2 may activate ECs,causing the inflow of extracellular calcium or the release of calciumfrom intracellular *** intracellar Ca2+may bind with calmodulin to activate phos-pholipase A2,thus initiating PAF synthesis and promoting EC-PMN adhesion.

关键词： endothelial cells vascular hydrogen peroxide platelet-activating factor leukocyte adhesion phospholipase A bovine

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The actions,detection and synthesis of platelet-activating factor (PAF) in mammalian pregnancy

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Journal of Forestry Research 1998年第4期9卷 283-287页

作者：刘玉堂隋淑芹孙中武毕冰许翠清 College of Wildlife Resources Northeast Forestry University Harbin P. R. China Harbin Grain Bureau China

platelet-activating factor (PAF) exhibits a variety of biological activities and it be thought to involved in various pathophysiological process. In this paper, some studies were summarized about those roles ofPAF in a variety productive processes of female of mammalian that inctude fertilization, implantation and parturition, and that was involved in the concentration, synthesis, deiradation and some assay methods of PAF. Therelationship between PAF and early pregnancy factor (EPF) was reviewed.

关键词： platelet-activating factor Mammalian Pregnancy Early pregnancy factor

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The inhibitory effects of β-adrenoceptor activation on vascular permeability increment induced by platelet-activating factor and histamine

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Journal of Medical Colleges of PLA(China) 1994年第2期9卷 112-115页

作者：蒋美珍李少华张亚霏丁自强

The effects of isoproterenol (IPN) on histamine and platelet-activating factor (PAF)-induced vascular permeability increment in rat skin and in cultured confluent endothelial cell monolayer were investigated. The results showed that after intravenous administration of 20 mg/kg Evans blue (EB) dye, the intradermal injection of 0. 2 ml PAF(10-7mol/L) or histamine (0. 5 mmol/L) could induce the exudation of 16. 82+2. 05 μg/g tissue and 21. 86+2. 86μg/g tissue of EB respectively into the injected skin. Pretreatment of the rats with intravenous IPN (10 μg/kg) decreased the EB exudation by 56. 2% and 43. 6% respectively. Propranolol (PPN), a β-adrenoceptor blocker, reversed the inhibitory effects of IPN. In rats treated with PPN alone, intradermal injection of PAF and histamine induced significant increase of skin EB exudation in comparison with the control, indicating that catecholamines at physiologic concentration in vivo may have inhibitory effects on vascular permeability. When cultured endothelial cell monolayers were perfused with 1% albumin in Hanks' balanced salt solution the increased fluid flux and protein clearance caused by PAF were significantly decreased by IPN pretreatment. The results confirmed the inhibitory effects of IPN on vascular permeability increment induced by PAF at the cellular level.

关键词： platelet-activating factor histamine isoproterenol propranolol edema rats

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The PARF Antagonist AChE Inhibitor PMS777 Attenuates LPS-Induced Acute Neuroinflammation

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Neuroscience & Medicine 2011年第4期2卷 355-362页

作者： Jin-Jia Hu Juan Li Zhang Wei Hong-Yu Gu Bi-Yun Shao Ding Wen Long Hong-Zhuan Chen 不详

When injected into the fourth ventricle, the proinflammagen lipopolysaccharide (LPS) induces acute neuroinflammation in the whole brain of rats. The new compound PMS777 is a novel platelet-activating factor receptor (PAFR) antagonist and acetylcholinesterase (AChE) inhibitor. The current study determined whether PMS777 could provide neuroprotection from the cytotoxic effects associated with LPS-induced neuroinflammation. Acute LPS infusions impaired recognition in rats as measured by the Morris water maze. In addition, LPS infusions decreased the number of AChE positive cells, and increased the number of OX-42 immunoreactive microglia and GFAP immunoreactive astrocytes in the hippocampus, the cortex and the basal nuclei. Furthermore, acute infusions of LPS also impaired organelles associated with protein synthesis. Peripheral administration of PMS777 (i.e., intraperitoneal injection) protected against the impairment in recognition, and attenuated the cytotoxic effects of the acute inflammatory processes upon cholinergic cells, microglia, astrocytes and ultrastructure of hippocampal cells. Here, we propose that the cytotoxic effects of acute neuroinflammation may involve the release of PAF and loss of cholinergic neurons, and this mechanism leads to neuronal dysfunction and spatial memory impairment. The PAFR antagonist inhibitor and AChE inhibitor PMS777 could provide neuroprotection from the cytotoxic effects induced by LPS.

关键词： Neuroinflammation Spatial Memory Acetylcholinesterase platelet-activating Factor Ultrastrurctural Analysis

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Inhibitory effects of isoproterenol on PAF-induced endothelial cell permeability and morphological changes

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Science China(Life Sciences) 1996年第1期39卷 80-86页

作者：丁自强李少华吴中立 Department of Pathophysiology Second Military Medical University Shanghai 200433 China

Using a model to study vascular permeability under hydrostatically perfused bovine pulmonary artery endothelial cell (EC) monolayers and a software to automatically analyse cell morphological parameters in a computer image workstation, the effects of isoproterenol (IPN) on platelet-activating factor (PAF)-induced changes in EC monolayer permeability and cell morphological parameters were studied. Albumin has the fortifying effect on endothelial barrier function. After treatment of EC monolayer with 10-8mol/L PAF, trans-monolayer permeability increased, cell surface area decreased, and intercellular space enlarged. As pretreatment with 10-4mol/L IPN, PAF-induced EC permeability increment and morphological changes were blocked. The results suggest that EC contraction and intercellular gap expansion are important mechanisms for PAF-induced high vascular permeability. IPN inhibits the effects of PAF via stabilization of EC morphology and prevention of intercellular gap formation.

关键词： vascular permeability catecholamine platelet-activating factor endothelial cell image processing.

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