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对大鼠急性给予镉会在脾脏中产生免疫抑制和促炎作用。

Acute cadmium administration to rats exerts both immunosuppressive and proinflammatory effects in spleen.

作者信息

Demenesku Jelena, Mirkov Ivana, Ninkov Marina, Popov Aleksandrov Aleksandra, Zolotarevski Lidija, Kataranovski Dragan, Kataranovski Milena

机构信息

Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, 142 Bulevar despota Stefana, 11000 Belgrade, Serbia.

Institute of Pathology, Military Medical Academy, 17Crnotravska 11000 Belgrade, Serbia.

出版信息

Toxicology. 2014 Dec 4;326:96-108. doi: 10.1016/j.tox.2014.10.012. Epub 2014 Oct 27.

Abstract

Conflicting data (both suppression and augmentation as well as lack of the effect) exist in respect to cadmium (Cd) and splenic T cell-based immune cell activity. Spleen is also the site of innate immune responses but impact of Cd on this type of immunity has been less explored. In the present study the effects of acute Cd administration on basic aspects of both T cell-based and innate immune spleen cell activity were examined in rats. Intraperitoneal injection of 1mg of Cd/kg resulted in decrease in concanavalin A (ConA) induced proliferation which seems to be more related to altered spleen cells responsiveness to IL-2 than to apoptosis. Differential effects on proinflammatory T cell derived cytokines were observed (decreases of IFN-γ gene expression and ConA-stimulated production, but increases in IL-17 mRNA levels with no effect on concentrations of protein product). Reduction of IFN-γ production seemed not to rely on IL-4 and IL-10, but at least partly on nitric oxide (NO). Increased activity relevant for innate immunity (granulocyte and CD11b(+) cell accumulation in the spleen, inducible nitric oxide synthase/iNOS expression and NO production by spleen cells) was observed, but there was a decrease in respiratory burst (dihydrorhodamine/DHR oxidation and nitroblue tetrazolium/NBT reduction). Increases of TNF-α and IL-1β gene expression and IL-1β protein product were noted as well. Administration of 0.5mg Cd/kg resulted in less pronounced (ConA-induced proliferation) or lack of the effect (IFN-γ production) on spleen T cell activities and on innate activities (granulocyte accumulation, NO production) as well. However, increases of spleen cell respiratory burst activity and IL-1β production were observed. Effects of lower cadmium doses (5ppm and 50ppm) on several aspects of spleen cell immune activity were observed in intermediate period of exposure (30 days, oral intake) as well. Differential effects of Cd on immune activities of spleen cells might contribute to our understanding of the complexity of immunomodulatory effects of this metal.

摘要

关于镉(Cd)与基于脾T细胞的免疫细胞活性,存在相互矛盾的数据(包括抑制、增强以及无效应)。脾脏也是固有免疫反应的场所,但镉对这类免疫的影响鲜有研究。在本研究中,检测了急性给予镉对大鼠基于T细胞的免疫和固有免疫脾细胞活性基本方面的影响。腹腔注射1mg Cd/kg导致伴刀豆球蛋白A(ConA)诱导的增殖减少,这似乎更多地与脾细胞对白细胞介素-2(IL-2)反应性的改变有关,而非细胞凋亡。观察到对促炎T细胞衍生细胞因子的不同影响(干扰素-γ(IFN-γ)基因表达和ConA刺激的产生减少,但白细胞介素-17(IL-17)mRNA水平增加,而对蛋白质产物浓度无影响)。IFN-γ产生的减少似乎不依赖于IL-4和IL-10,但至少部分依赖于一氧化氮(NO)。观察到与固有免疫相关的活性增加(脾脏中粒细胞和CD11b(+)细胞的积累、诱导型一氧化氮合酶/iNOS的表达以及脾细胞产生NO),但呼吸爆发减少(二氢罗丹明/DHR氧化和硝基蓝四唑/NBT还原)。还注意到肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)基因表达以及IL-1β蛋白质产物增加。给予0.5mg Cd/kg对脾T细胞活性和固有活性(粒细胞积累、NO产生)的影响不那么明显(ConA诱导的增殖)或无效应(IFN-γ产生)。然而,观察到脾细胞呼吸爆发活性和IL-1β产生增加。在暴露中期(30天,经口摄入)也观察到较低镉剂量(5ppm和50ppm)对脾细胞免疫活性多个方面的影响。镉对脾细胞免疫活性的不同影响可能有助于我们理解这种金属免疫调节作用的复杂性。

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