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布瑞索抑制磷酸二酯酶 4 基因表达,并调节人单核细胞中选择的炎症介质水平。

Bresol inhibits phosphodiesterase 4 gene expression and modulates the levels of select mediators of inflammation in human monocytic cells.

机构信息

Department of Cell biology and Immunology, Research and Development, The Himalaya Drug Company, Bangalore, India.

出版信息

J Immunotoxicol. 2011 Oct-Dec;8(4):315-23. doi: 10.3109/1547691X.2011.603389. Epub 2011 Aug 19.

Abstract

Bresol-a poly-herbal formulation, has been reported to be effective against bronchial asthma and allergic rhinitis in children. In vivo studies have supported the anti-histaminic and anti-anaphylactic action of bresol. However, the mechanism of action of bresol in modulation of inflammation has not been studied at the cellular and molecular level. The present study was aimed to elucidate the mechanism(s) of action of bresol at the cellular and molecular levels, using human monocyte leukemia cells. The effects of bresol on phosphodiesterase 4B (PDE4B) gene expression were analyzed using human monocytic U937 leukemia cells. The ability of bresol to stimulate cAMP formation in these cells, as well as its effects on mediators of inflammation like tumor necrosis factor-α (TNFα), nitric oxide (NO), and cycloxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated U937 cells, were also studied. The results here indicated that bresol exhibited potential anti-inflammatory properties by inhibiting LPS-induced PDE4B gene expression in the cells. Bresol also dose dependently activated cAMP formation, and inhibited TNFα, NO, as well as COX-2 formation in the LPS-stimulated cells. Based upon the results, we concluded that the reported anti-inflammatory activity of bresol might be attributed to its abilities to inhibit PDE4B and thus elevate cAMP levels in human monocytes. The anti-inflammatory effects of bresol might also be a result of the capacity of bresol to modulate the formation of TNFα, NO, and COX-2 in monocytes.

摘要

Bresol 是一种复方草药制剂,据报道对儿童支气管哮喘和过敏性鼻炎有效。体内研究支持 Bresol 的抗组胺和抗过敏作用。然而,Bresol 调节炎症的作用机制尚未在细胞和分子水平上进行研究。本研究旨在阐明 Bresol 在细胞和分子水平上的作用机制,使用人单核白血病细胞。使用人单核细胞白血病 U937 细胞分析 Bresol 对磷酸二酯酶 4B(PDE4B)基因表达的影响。研究 Bresol 刺激这些细胞中环磷酸腺苷(cAMP)形成的能力,以及其对炎症介质如肿瘤坏死因子-α(TNFα)、一氧化氮(NO)和环加氧酶-2(COX-2)的影响在脂多糖(LPS)刺激的 U937 细胞中。结果表明,Bresol 通过抑制细胞中 LPS 诱导的 PDE4B 基因表达表现出潜在的抗炎特性。Bresol 还剂量依赖性地激活 cAMP 形成,并抑制 LPS 刺激细胞中 TNFα、NO 和 COX-2 的形成。基于这些结果,我们得出结论,报道的 Bresol 的抗炎活性可能归因于其抑制 PDE4B 的能力,从而提高人单核细胞中的 cAMP 水平。Bresol 的抗炎作用也可能是 Bresol 调节 TNFα、NO 和 COX-2 在单核细胞中形成的能力的结果。

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