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Involvement of cysteinyl leukotriene signaling in microglial morphological changes and CASP1 expression in vitro

中国药理学与毒理学杂志 2017年第10期31卷 1028-1029页

作者： Yu-xi WANG Si-ran ZHANG Xue XU Cheng-tan LI Wei ZHENG Jian-bo ZHAO Yan-fang WANG Li-hui ZHANG Department of Pharmacology Hangzhou Key Laboratory of Medical NeurobiologySchool of MedicineHangzhou Normal University Department of Neurology Zhejiang Hospital

OBJECTIVE We have recently reported that cysteinyl leukotriene(Cys LT) signaling plays an important role in microglial interleukin(IL)-1β secretion and subsequent *** present study aimed to examine microglial morphological changes and the upstream molecular underlying IL^(-1)β production in Cys LT receptor agonist leukotriene D4(LTD4)-treated BV2 microglia in *** Twenty-four hours after murine microglial BV2 cells were stimulated with LTD4(1-100 nmol·L^(-1)),the cell proliferation and morphology were *** expression level of cysteinyl aspartate-specific protease 1(CASP1) protein was measured by Western blotin BV2 *** addition,BV2 cells were pretreated with or without CysLT1 receptor antagonist montelukast for 1 h and the effects of monte-lukaston LTD4-stimulated microglial activation and CASP1 expression were *** The number of BV2 cells had an increasing tendency after 24 h treatment with LTD4,but no significant differences were observed between the control and LTD4-treated cells(P>0.05).Under basal and resting conditions,BV2 microglial cells displayed a ramified ***,LTD4 at 100 nmool·L^(-1) drove microglial morphological changes from a ramified towards an amoeboid *** expression of CASP1 protein was significantly upregulated in 100 nmool·L^(-1) LTD4-treated BV2 microglia(P<0.01).Furthermore,pretreatment with CysLT1 receptor antagonist montelukast prevented cell morphological changes and suppressed the increased CASP1 expression in LTD4-treated BV2 cells(P<0.05).CONCLUSION Cys LT receptor agonist LTD4 induces morphological changes and CASP1 expressionin BV2 microglia,which can be inhibited by CysLT1 *** results suggest the involvement of Cys LT signaling in microglial morphological changes and CASP1 expression.

关键词： cysteinyl leukotriene receptor microglia inflammation

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Enhanced expressions and activations of leukotriene C4synthesis enzymes in D-galactosamine/lipopolysaccharide-induced rat fulminant hepatic failure model

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World Journal of Gastroenterology 2008年第17期14卷 2748-2756页

作者： Kui-Fen Ma Hong-Yu Yang Zhe Chen Luo-Yang Qi Dan-Yan Zhu Yi-Jia Lou Institute of Pharmacology & Toxicology andBiochemical Pharmaceutics College of Pharmaceutical SciencesZlaejiang University Hangzhou 310058 Zhejiang Province China

AIM： To investigate the expression and activity of leukotriene C4 （LTC4） synthesis enzymes and their underlying relationship with cysteinyl leukotriene （cys-LT） generation in a rat fulminant hepatic failure （FHF） model induced by D-galactosamine/lipopolysaccharide （D-GaIN/ LPS）. METHODS： Rats were treated with D-GaIN （300 mg/kg） plus LPS （0.1 mg/kg） for 1, 3, 6, and 12 h. Enzyme immunoassay was used to determine the hepatic cys-LT content. Reverse transcription-polymerase chain reaction （RT-PCR）, Western blot or immunohistochemical assay were employed to assess the expression or location of LTC4 synthesis enzymes, which belong to membrane associated proteins in eicosanoid and glutathione （MAPEG） metabolism superfamily. Activity of LTC4 synthesis enzymes was evaluated by determination of the products of LTA4 after incubation with liver microsomes using high performance liquid chromatography （HPLC）. RESULTS： Livers were injured after treatment with D-GaIN/LPS, accompanied by cys-LT accumulation at the prophase of liver injury. Both LTC4 synthase （LTC4S） and microsomal glutathione-S-transferase （mGST） 2 were expressed in the rat liver, while the latter was specifically located in hepatocytes. Their mRNA and protein expressions were up-regulated at an earlier phase after treatment with D-GaIN/LPS. Meantime, a higher activity of LTC4 synthesis enzymes was detected, although theactivity of LTC4S played the main role in this case. CONCLUSION： The expression and activity of both LTC4S and mGST2 are up regulated in a rat FHF model, which are, at least, partly responsible for cys-LT hepatic accumulation.

关键词： cysteinyl leukotriene Micmsomal glutathioneS-transferase 2 leukotriene C4 synthase D-galacto-samine/lipopolysaccharide Fulminant hepatic failure

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