Bromosulfophthalein suppresses inflammatory effects in lipopolysaccharide-stimulated RAW264.7 macrophages.
Bromosulfophthalein suppresses inflammatory effects in lipopolysaccharide-stimulated RAW264.7 macrophages.
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DOI：
10.1080/08923973.2020.1808985
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发表时间：
2020-10
影响因子：
3.3
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Cui F;Sequeira SB;Huang Z;Shang G;Cui Q;Yang X
据报道，细胞中最丰富的抗氧化剂谷胱甘肽（GSH）可以抑制活化的巨噬细胞产生促炎细胞因子。溴磺酞（BSP）已被认为是减少GSH从细胞外排的抑制剂，导致细胞内GSH水平升高。在这项研究中，我们首次评估了BSP是否对脂多糖（LPS）刺激的巨噬细胞具有抗炎作用。用BSP处理RAW 264.7细胞，评估促炎细胞因子、谷胱甘肽和亚硝酸盐的水平。采用定量RT-PCR分析诱导型一氧化氮合酶（iNOS）、肿瘤坏死因子α (TNF α)、白细胞介素-1β (IL-1β)和白细胞介素-6 （IL-6）的基因表达。我们还通过Western blot和流式细胞术分析了各种炎症信号通路，包括Akt/forkhead box protein O1 (FoxO1)/ toll样受体4 （TLR4）、丝裂原活化蛋白激酶（MAPKs）和Fas蛋白。我们的研究表明，BSP诱导lps刺激的巨噬细胞细胞内GSH水平升高。BSP抑制一氧化氮和促炎细胞因子的产生。BSP增加Akt的磷酸化和fox01的核排斥，抑制TLR4的表达。此外，BSP降低了MAPKs的激活和Fas的表达。综上所述，这些数据表明BSP可以通过多种信号通路减轻炎症。这些发现突出了BSP作为一种新型抗炎剂的潜力。
It has been reported that glutathione (GSH), the most abundant cellular antioxidant, can inhibit production of pro-inflammatory cytokines by activated macrophages. Bromosulfophthalein (BSP) has been recognized as an inhibitor of the efflux of reduced GSH from cells, leading to an increase in the intracellular GSH level. In this study, we evaluated, for the first time, whether BSP possessed anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated macrophages. RAW 264.7 cells were treated with BSP and the levels of proinflammatory cytokines, GSH, and nitrite were assessed. Gene expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) was analyzed via quantitative RT-PCR. We also examined various inflammatory signaling pathways including Akt/forkhead box protein O1 (FoxO1)/ toll-like receptor 4 (TLR4), mitogen-activated protein kinases (MAPKs) and Fas proteins by Western blot and flow cytometry analysis. Our study demonstrated that BSP induced an increase in intracellular GSH levels in LPS-stimulated macrophages. BSP inhibited production of nitric oxide and proinflammatory cytokines. BSP increased phosphorylation of Akt and nuclear exclusion of FoxO1 and suppressed TLR4 expression. Additionally, BSP decreased MAPKs activation and Fas expression. Taken together, these data suggest that BSP can attenuate inflammation through multiple signaling pathways. These findings highlightthe potential of BSP as a new anti-inflammatory agent.
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影响因子：
4.8
作者：
Pullar, JM;Hampton, MB
通讯作者：
Hampton, MB
影响因子：
4.1
作者：
Emre, Yalin;Hurtaud, Corinne;Cassard-Doulcier, Anne-Marie
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影响因子：
11.4
作者：
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通讯作者：
Olefsky, Jerrold M.
影响因子：
2.9
作者：
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通讯作者：
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6.7
作者：
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通讯作者：
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