Coumarins belong to a diverse group of naturally occurring non-nutrient phytochemicals known as benzo-α- pyrones. In this study, esculetin, a 6,7-dihydroxy derivative of coumarin with pleiotropic biological activitie...Coumarins belong to a diverse group of naturally occurring non-nutrient phytochemicals known as benzo-α- pyrones. In this study, esculetin, a 6,7-dihydroxy derivative of coumarin with pleiotropic biological activities, was found to have no significant cytotoxic effect on normal murine macrophages, but it could increase the in vivo migration of the thioglycollate-elicited macrophages in a dose-dependent manner. Moreover, esculetin significantly increased the endocytic activity, and augmented the nitric oxide production and iNOS gene expression in LPS-treated macrophages. In addition, in vivo administration of esculetin into mice was shown to increase the mitogenesis of splenic lymphocytes towards Con A and LPS stimulations, and induced the LAK activity of splenic lymphocytes. Collectively, our results indicate that esculetin could exert immunomodulatory effects on murine macrophages and lymphocytes, both in vitro and in vivo, and this might be one of the possible mechanisms by which coumarins can exert their chemopreventive and anti-tumor activities in vivo. Cellular ＆ Molecular Immunology. 2005;2（3）： 181-188.展开更多
本研究旨在探讨A类Ⅰ型清道夫受体(scavenger receptor class A type Ⅰ,SR-AI)在呼吸道感染常见病原体肺炎克雷伯菌及铜绿假单胞菌感染过程中的免疫调节功能。以肺炎克雷伯菌和铜绿假单胞菌临床分离株与野生型小鼠和SR-AI^(-/-)小鼠腹...本研究旨在探讨A类Ⅰ型清道夫受体(scavenger receptor class A type Ⅰ,SR-AI)在呼吸道感染常见病原体肺炎克雷伯菌及铜绿假单胞菌感染过程中的免疫调节功能。以肺炎克雷伯菌和铜绿假单胞菌临床分离株与野生型小鼠和SR-AI^(-/-)小鼠腹腔原代巨噬细胞互作,研究SR-AI在吞噬和炎症反应中的作用。荧光染料染色菌体及检测胞内荧光强度,数据显示SR-AI敲除后巨噬细胞对肺炎克雷伯菌的吞噬能力下降,但对铜绿假单胞菌的吞噬能力升高。采用实时定量荧光聚合酶链反应检测相关炎症因子mRNA水平,发现SRAI敲除后肺炎克雷伯菌和铜绿假单胞菌刺激巨噬细胞引发的炎症反应均增强。结果表明,SR-AI参与巨噬细胞对肺炎克雷伯菌的吞噬,但不参与对铜绿假单胞菌的吞噬,且可能抑制了肺炎克雷伯菌和铜绿假单胞菌引发的炎症反应。展开更多
目的通过研究解毒祛瘀滋肾方对Cp G寡脱氧核苷酸(Cp G oligodeoxynucletide,Cp G ODN)刺激后小鼠单核巨噬细胞Toll样受体9(Toll like receptor 9,TLR9)信号通路的影响,探讨解毒祛瘀滋肾方治疗系统性红斑狼疮(systemic lupus erythematos...目的通过研究解毒祛瘀滋肾方对Cp G寡脱氧核苷酸(Cp G oligodeoxynucletide,Cp G ODN)刺激后小鼠单核巨噬细胞Toll样受体9(Toll like receptor 9,TLR9)信号通路的影响,探讨解毒祛瘀滋肾方治疗系统性红斑狼疮(systemic lupus erythematosus,SLE)增效减毒的机制。方法体外培养小鼠单核巨噬细胞,随机分为空白血清组、Cp G ODN刺激组、Cp G ODN加地塞米松组及Cp G ODN加含药血清组。干预24 h后收集细胞,采用RT-PCR法检测TLR9、髓样分化因子88(My D88)、核转录因子-κB(NF-κB)及干扰素-α(IFN-α)mRNA的表达;Western blot法检测TLR9、NF-κB蛋白表达;双荧光素酶报告基因分析NF-κB转录活力的变化。结果与空白血清组比较,Cp G ODN刺激组TLR9、My D88、NF-κB、IFN-αmRNA表达、TLR9、NFκ-B蛋白表达和NF-κB转录活力均升高,差异有统计学意义(P<0.05,P<0.01);与Cp G ODN刺激组比较,Cp G ODN加地塞米松组My D88、NF-κB、IFN-αmRNA表达、NF-κB蛋白表达和NF-κB转录活力均下降,差异有统计学意义(P<0.01),Cp G ODN加含药血清组TLR9、My D88、NF-κB、IFN-αmRNA、TLR9、NFκ-B蛋白表达和NF-κB转录活力均下降,差异有统计学意义(P<0.01)。结论解毒祛瘀滋肾方治疗SLE所起到增效减毒的作用可能是通过调控TLR9信号通路来实现的。展开更多
<em>Background:</em> Antisense peptide nucleic acids (PNAs) exhibit growth inhibitory effects on bacteria by inhibiting the expression of essential genes and could be promising therapeutic agents for treat...<em>Background:</em> Antisense peptide nucleic acids (PNAs) exhibit growth inhibitory effects on bacteria by inhibiting the expression of essential genes and could be promising therapeutic agents for treating bacterial infections. A study was carried out to determine the efficacy of several antisense PNAs in inhibiting extracellular and intracellular growth of <em>Mycobacterium smegmatis</em>. <em>Methods: </em>Six PNAs obtained from a commercial supplier were tested to evaluate the inhibitory effect on bacterial growth by inhibiting the expression of the following essential genes: <em>inhA </em>(a fatty acid elongase), <em>rpsL</em> (ribosomal S12 protein), <em>gyrA</em> (DNA gyrase), <em>pncA</em> (pyrazinamidase), <em>polA</em> (DNA polymerase I) and <em>rpoC</em> (RNA polymerase <em>β</em> subunit) of <em>M. smegmatis</em>. Each PNA was tested at 20 μM, 10 μM, 5 μM and 2.5 μM concentrations to determine whether they caused a dose dependent killing of <em>M. smegmatis</em> cultured in Middlebrook 7H9 broth or in a J774A.1 murine macrophage cell line.<em> Results:</em> In Middlebrook broth, the strong growth inhibitory effect against <em>M. smegmatis</em> was observed by PNAs targeting the <em>inhA </em>and <em>rpsL</em> genes at all four concentrations. The PNAs targeting the<em> pncA</em>, <em>polA</em> and<em> rpoC</em> genes were found to exhibit strong growth inhibition against <em>M. smegmatis</em> but only at 20 μM concentration. No growth inhibition of <em>M. smegmatis </em>was seen in pure culture when treated with PNAs targeting gyrA and a mismatch PNA targeting dnaG (DNA primase). All six PNAs showed killing of <em>M. smegmatis </em>in J774A.1 macrophage cell line that were statistically significant (p < 0.05). <em>Conclusion:</em> It may be concluded from this study that PNAs could be potential therapeutics for mycobacterial infections.展开更多
文摘Coumarins belong to a diverse group of naturally occurring non-nutrient phytochemicals known as benzo-α- pyrones. In this study, esculetin, a 6,7-dihydroxy derivative of coumarin with pleiotropic biological activities, was found to have no significant cytotoxic effect on normal murine macrophages, but it could increase the in vivo migration of the thioglycollate-elicited macrophages in a dose-dependent manner. Moreover, esculetin significantly increased the endocytic activity, and augmented the nitric oxide production and iNOS gene expression in LPS-treated macrophages. In addition, in vivo administration of esculetin into mice was shown to increase the mitogenesis of splenic lymphocytes towards Con A and LPS stimulations, and induced the LAK activity of splenic lymphocytes. Collectively, our results indicate that esculetin could exert immunomodulatory effects on murine macrophages and lymphocytes, both in vitro and in vivo, and this might be one of the possible mechanisms by which coumarins can exert their chemopreventive and anti-tumor activities in vivo. Cellular ＆ Molecular Immunology. 2005;2（3）： 181-188.
文摘本研究旨在探讨A类Ⅰ型清道夫受体(scavenger receptor class A type Ⅰ,SR-AI)在呼吸道感染常见病原体肺炎克雷伯菌及铜绿假单胞菌感染过程中的免疫调节功能。以肺炎克雷伯菌和铜绿假单胞菌临床分离株与野生型小鼠和SR-AI^(-/-)小鼠腹腔原代巨噬细胞互作,研究SR-AI在吞噬和炎症反应中的作用。荧光染料染色菌体及检测胞内荧光强度,数据显示SR-AI敲除后巨噬细胞对肺炎克雷伯菌的吞噬能力下降,但对铜绿假单胞菌的吞噬能力升高。采用实时定量荧光聚合酶链反应检测相关炎症因子mRNA水平,发现SRAI敲除后肺炎克雷伯菌和铜绿假单胞菌刺激巨噬细胞引发的炎症反应均增强。结果表明,SR-AI参与巨噬细胞对肺炎克雷伯菌的吞噬,但不参与对铜绿假单胞菌的吞噬,且可能抑制了肺炎克雷伯菌和铜绿假单胞菌引发的炎症反应。
文摘目的通过研究解毒祛瘀滋肾方对Cp G寡脱氧核苷酸(Cp G oligodeoxynucletide,Cp G ODN)刺激后小鼠单核巨噬细胞Toll样受体9(Toll like receptor 9,TLR9)信号通路的影响,探讨解毒祛瘀滋肾方治疗系统性红斑狼疮(systemic lupus erythematosus,SLE)增效减毒的机制。方法体外培养小鼠单核巨噬细胞,随机分为空白血清组、Cp G ODN刺激组、Cp G ODN加地塞米松组及Cp G ODN加含药血清组。干预24 h后收集细胞,采用RT-PCR法检测TLR9、髓样分化因子88(My D88)、核转录因子-κB(NF-κB)及干扰素-α(IFN-α)mRNA的表达;Western blot法检测TLR9、NF-κB蛋白表达;双荧光素酶报告基因分析NF-κB转录活力的变化。结果与空白血清组比较,Cp G ODN刺激组TLR9、My D88、NF-κB、IFN-αmRNA表达、TLR9、NFκ-B蛋白表达和NF-κB转录活力均升高,差异有统计学意义(P<0.05,P<0.01);与Cp G ODN刺激组比较,Cp G ODN加地塞米松组My D88、NF-κB、IFN-αmRNA表达、NF-κB蛋白表达和NF-κB转录活力均下降,差异有统计学意义(P<0.01),Cp G ODN加含药血清组TLR9、My D88、NF-κB、IFN-αmRNA、TLR9、NFκ-B蛋白表达和NF-κB转录活力均下降,差异有统计学意义(P<0.01)。结论解毒祛瘀滋肾方治疗SLE所起到增效减毒的作用可能是通过调控TLR9信号通路来实现的。
文摘<em>Background:</em> Antisense peptide nucleic acids (PNAs) exhibit growth inhibitory effects on bacteria by inhibiting the expression of essential genes and could be promising therapeutic agents for treating bacterial infections. A study was carried out to determine the efficacy of several antisense PNAs in inhibiting extracellular and intracellular growth of <em>Mycobacterium smegmatis</em>. <em>Methods: </em>Six PNAs obtained from a commercial supplier were tested to evaluate the inhibitory effect on bacterial growth by inhibiting the expression of the following essential genes: <em>inhA </em>(a fatty acid elongase), <em>rpsL</em> (ribosomal S12 protein), <em>gyrA</em> (DNA gyrase), <em>pncA</em> (pyrazinamidase), <em>polA</em> (DNA polymerase I) and <em>rpoC</em> (RNA polymerase <em>β</em> subunit) of <em>M. smegmatis</em>. Each PNA was tested at 20 μM, 10 μM, 5 μM and 2.5 μM concentrations to determine whether they caused a dose dependent killing of <em>M. smegmatis</em> cultured in Middlebrook 7H9 broth or in a J774A.1 murine macrophage cell line.<em> Results:</em> In Middlebrook broth, the strong growth inhibitory effect against <em>M. smegmatis</em> was observed by PNAs targeting the <em>inhA </em>and <em>rpsL</em> genes at all four concentrations. The PNAs targeting the<em> pncA</em>, <em>polA</em> and<em> rpoC</em> genes were found to exhibit strong growth inhibition against <em>M. smegmatis</em> but only at 20 μM concentration. No growth inhibition of <em>M. smegmatis </em>was seen in pure culture when treated with PNAs targeting gyrA and a mismatch PNA targeting dnaG (DNA primase). All six PNAs showed killing of <em>M. smegmatis </em>in J774A.1 macrophage cell line that were statistically significant (p < 0.05). <em>Conclusion:</em> It may be concluded from this study that PNAs could be potential therapeutics for mycobacterial infections.
