Interactions among type I and type II interferon, tumor necrosis factor, and beta-estradiol in the regulation of immune response-related gene expressions in systemic lupus erythematosus.
Interactions among type I and type II interferon, tumor necrosis factor, and beta-estradiol in the regulation of immune response-related gene expressions in systemic lupus erythematosus.
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DOI：
10.1186/ar2584
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发表时间：
2009
影响因子：
4.9
通讯作者：
Nishimoto N
中科院分区：
文献类型：
--
作者：
Lee HM;Mima T;Sugino H;Aoki C;Adachi Y;Yoshio-Hoshino N;Matsubara K;Nishimoto N
系统性红斑狼疮（SLE）是一种典型的自身免疫性疾病，具有多种临床表现。尽管病因仍不清楚，但多种细胞因子在 SLE 中相互作用并发挥病理作用。在本研究中，我们研究了 SLE 患者外周血中表达的免疫反应相关分子网络，以及细胞因子相互作用对这些分子调节的影响。使用 DNA 微阵列分析来分析 SLE 患者和健康女性外周血的基因表达谱。选择属于免疫反应类别的差异表达基因并使用生物信息学工具进行分析。由于TNF、IFNγ、β-雌二醇（E2）和IFNα之间的相互作用可能调节干扰素诱导（IFI）基因的表达，因此对外周血单核细胞进行刺激和共刺激实验，然后使用定量RT-PCR进行分析。在免疫反应的功能类别中鉴定出 38 个下调基因和 68 个上调基因。在 SLE 患者外周血中证实了过度表达的 IFI 基因。通过对这些基因进行基于网络的分析，构建了包括细胞因子（例如 TNF 和 IFNγ）和 E2 在内的多个网络。 TNF调节的基因在这些网络中占主导地位，但对外周血单核细胞的体外TNF刺激显示SLE和健康个体之间上述基因表达没有差异。与 IFNα 和 TNF、IFNγ 或 E2 之一共同刺激表明，TNF 具有抑制作用，而 IFNγ 本质上对体外 IFI 基因表达具有协同作用。 E2 对三个个体中的 IFI 基因表达表现出不同的影响。 TNF可能抑制SLE中IFNα的异常调节，而IFNγ可能具有协同作用。 IFNα 与 TNF、IFNγ 或 E2 之一之间的相互作用似乎参与了 SLE 的发病机制。
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by various clinical manifestations. Several cytokines interact and play pathological roles in SLE, although the etiopathology is still obscure. In the present study we investigated the network of immune response-related molecules expressed in the peripheral blood of SLE patients, and the effects of cytokine interactions on the regulation of these molecules. Gene expression profiles of peripheral blood from SLE patients and from healthy women were analyzed using DNA microarray analysis. Differentially expressed genes classified into the immune response category were selected and analyzed using bioinformatics tools. Since interactions among TNF, IFNγ, β-estradiol (E2), and IFNα may regulate the expression of interferon-inducible (IFI) genes, stimulating and co-stimulating experiments were carried out on peripheral blood mononuclear cells followed by analysis using quantitative RT-PCR. Thirty-eight downregulated genes and 68 upregulated genes were identified in the functional category of immune response. Overexpressed IFI genes were confirmed in SLE patient peripheral bloods. Using network-based analysis on these genes, several networks including cytokines – such as TNF and IFNγ – and E2 were constructed. TNF-regulated genes were dominant in these networks, but in vitro TNF stimulation on peripheral blood mononuclear cells showed no differences in the above gene expressions between SLE and healthy individuals. Co-stimulating with IFNα and one of TNF, IFNγ, or E2 revealed that TNF has repressive effects while IFNγ essentially has synergistic effects on IFI gene expressions in vitro. E2 showed variable effects on IFI gene expressions among three individuals. TNF may repress the abnormal regulation by IFNα in SLE while IFNγ may have a synergistic effect. Interactions between IFNα and one of TNF, IFNγ, or E2 appear to be involved in the pathogenesis of SLE.
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DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V
影响因子：
20.3
作者：
Hayashi, F;Means, TK;Luster, AD
通讯作者：
Luster, AD
影响因子：
20.3
作者：
Goebeler, M;Kilian, K;Ludwig, S
通讯作者：
Ludwig, S
影响因子：
56.9
作者：
Blanco, P;Palucka, AK;Banchereau, J
通讯作者：
Banchereau, J
影响因子：
4.1
作者：
Ishii, Taeko;Onda, Hiroaki;Nojima, Hiroshi
通讯作者：
Nojima, Hiroshi