Functional consequences of the SHP-1 defect in motheaten viable mice:: Role of NF-κB
Functional consequences of the SHP-1 defect in motheaten viable mice:: Role of NF-κB
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DOI：
10.1006/cimm.1998.1272
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发表时间：
1998-04-10
影响因子：
4.3
通讯作者：
Schiffenbauer, J
中科院分区：
文献类型：
--
作者：
Khaled, AR;Butfiloski, EJ;Schiffenbauer, J
为了确定 src 同源域 1 蛋白 (SHP-1) 缺陷的功能后果，我们检查了受害存活 (Mev) 小鼠的细胞因子产生和 NF-κ B 活性。我们发现与同窝对照成年小鼠相比，Mev 小鼠血清和培养的 B 细胞和 T 细胞中白细胞介素 6 (IL-6)、白细胞介素 10 (IL-10)、肿瘤坏死因子 (TNF) 和干扰素 γ (IFN-γ) 水平升高。 Mev血清和活化的Mev T细胞中检测到的白细胞介素-a（IL-2）水平降低，但IL-2受体表达增加。然后我们评估了 NF-kappa B 的活性，发现该蛋白在 Mev B 和 T 细胞中高度表达。为了确定 NF-kappa B 是否在导致 Mev 小鼠细胞因子水平升高中发挥作用，我们用 NF-kappa B 诱饵处理活化的 Mev T 细胞，发现用诱饵处理细胞培养物导致 IL-6、GM-CSF 和 TNF 的分泌显着减少，但 IFN-γ 的分泌没有显着减少。因此，我们的数据表明，Mev 小鼠分泌的炎症细胞因子水平升高，这些细胞因子可能是 Mev 临床疾病发展的介质，并且 NF-κ B 在此过程中发挥重要作用，影响免疫反应的调节。 (C) 1998 年学术出版社。
To define the functional consequences of the src-homology domain-1 protein (SHP-1) defect, we examined cytokine production and NF-kappa B activity in motheaten viable (Mev) mice. We found elevated levels of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor (TNF), and interferon-gamma (IFN-gamma) in Mev mice sera and cultured B and T cells compared to littermate control adult mice. The levels of interleukin-a (IL-2) detected in Mev sera and activated Mev T cells were decreased, but IL-2 receptor expression was increased. We then evaluated the activity of NF-kappa B and found that this protein is highly expressed in Mev B and T cells. To determine if NF-kappa B had a role in causing the elevated levels of cytokines in Mev mice, we treated activated Mev T cells with an NF-kappa B decoy and found that cell culture treatment with the decoy resulted in significant reduction of the secretion of IL-6, GM-CSF, and TNF, but not IFN-gamma. Therefore, our data show that Mev mice secrete elevated levels of inflammatory cytokines, which can be mediators in the development of the Mev clinical disorder, and that NF-kappa B has an important role in this process, impacting upon the regulation of the immune response. (C) 1998 Academic Press.