Murine BAFF expression is up-regulated by estrogen and interferons: implications for sex bias in the development of autoimmunity.
Murine BAFF expression is up-regulated by estrogen and interferons: implications for sex bias in the development of autoimmunity.
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DOI：
10.1016/j.molimm.2012.06.013
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发表时间：
2013-01
影响因子：
3.6
通讯作者：
Choubey D
中科院分区：
文献类型：
--
作者：
Panchanathan R;Choubey D
系统性红斑狼疮(SLE)在患者和某些小鼠模型中表现出强烈的性别偏见。此外，在大多数患者中，血清I型干扰素(干扰素-α)水平的升高与疾病的严重程度有关。由于系统性红斑狼疮患者和小鼠模型中B细胞激活因子水平的升高与系统性红斑狼疮的发生发展有关，因此我们研究了雌激素雌激素和/或干扰素(干扰素-α或γ)对小鼠B细胞活化因子表达的调节作用。我们发现，从C57BL/6雌性小鼠分离的免疫细胞(CD11b+、CD11c+和CD19+)的BAFF mRNA和蛋白的稳态水平明显高于年龄匹配的雄性小鼠。免疫细胞经干扰素或E_2处理后，BAFF的mRNA和蛋白水平显著升高，而脾细胞雌激素受体α、IRF5或STAT1的表达缺失则降低了BAFF的表达。此外，用干扰素-α、干扰素-γ或E2处理RAW264.7巨噬细胞可诱导其表达BAFF。有趣的是，在RAW264.7细胞中，干扰素和雌激素诱导蛋白p202的表达增加，显著增加了BAFF的表达水平，并刺激了BAFF-Luc-Report的活性。因此，P202蛋白在狼疮易感小鼠B6.Nba2-ABC比非狼疮易感C57BL/6和B6.Nba2-C雌性小鼠中的表达增加与BAFF的表达水平有关。总之，我们的观察表明，雌激素和干扰素诱导的免疫细胞中p202蛋白水平的增加在一定程度上通过上调BAFF的表达而导致性别偏见。
Systemic lupus erythematosus (SLE) in patients and certain mouse models exhibits a strong sex bias. Additionally, in most patients, increased serum levels of type I interferon (IFN-α) are associated with severity of the disease. Because increased levels of B cell activating factor (BAFF) in SLE patients and mouse models are associated with the development of SLE, we investigated whether the female sex hormone estrogen (E2) and/or IFNs (IFN-α or γ) could regulate the expression of murine BAFF. We found that steady-state levels of BAFF mRNA and protein were measurably higher in immune cells (CD11b+, CD11c+, and CD19+) isolated from C57BL/6 females than the age-matched male mice. Treatment of immune cells with IFN or E2 significantly increased levels of BAFF mRNA and protein and a deficiency of estrogen receptor-α, IRF5, or STAT1 expression in splenic cells decreased expression of BAFF. Moreover, treatment of RAW264.7 macrophage cells with IFN-α, IFN-γ, or E2 induced expression of BAFF. Interestingly, increased expression of p202, an IFN and estrogen-inducible protein, in RAW264.7 cells significantly increased the expression levels of BAFF and also stimulated the activity of the BAFF-luc-reporter. Accordingly, the increased expression of the p202 protein in lupus-prone B6.Nba2-ABC than non lupus-prone C57BL/6 and B6.Nba2-C female mice was associated with increased expression levels of BAFF. Together, our observations demonstrated that estrogen and IFN-induced increased levels of the p202 protein in immune cells contribute to sex bias in part through up-regulation of BAFF expression.
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干扰素诱导的IFI200家族基因在全身性红斑狼疮中。
影响因子：
4.4
作者：
Choubey, Divaker;Panchanathan, Ravichandran
通讯作者：
Panchanathan, Ravichandran
影响因子：
5
作者：
Bynote, K. K.;Hackenberg, J. M.;Gould, K. A.
通讯作者：
Gould, K. A.
影响因子：
2.8
作者：
Moon, Eun-Yi;Park, Hyunsung
通讯作者：
Park, Hyunsung
DOI：
10.4049/jimmunol.0901322
发表时间：
2010-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jørgensen TN;Alfaro J;Enriquez HL;Jiang C;Loo WM;Atencio S;Bupp MR;Mailloux CM;Metzger T;Flannery S;Rozzo SJ;Kotzin BL;Rosemblatt M;Bono MR;Erickson LD
通讯作者：
Erickson LD
影响因子：
4.4
作者：
Harigai, Masayoshi;Kawamoto, Manabu;Miyasaka, Nobuyuki
通讯作者：
Miyasaka, Nobuyuki