Apolipoprotein E-knockout mice show increased titers of serum anti-nuclear and anti-dsDNA antibodies
Apolipoprotein E-knockout mice show increased titers of serum anti-nuclear and anti-dsDNA antibodies
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载脂蛋白 E 敲除小鼠血清抗核抗体和抗 dsDNA 抗体滴度增加
DOI：
10.1016/j.bbrc.2012.06.044
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发表时间：
2012-07-13
影响因子：
3.1
通讯作者：
Zhang, Yun
中科院分区：
文献类型：
--
作者：
Wang, Yuehai;Huang, Ziyang;Zhang, Yun
载脂蛋白e敲除（ApoE(-/-)）小鼠，动脉粥样硬化易感小鼠，表现出自身免疫反应，但其发病机制尚不完全清楚。我们研究了雌性和雄性ApoE（-/-）小鼠的发病机制。对所有ApoE（-/-）和C57BL/6 （B6）小鼠的脾脏称重。ELISA法检测血清IgG水平及抗核抗体（ANA）和抗双链DNA （anti-dsDNA）抗体滴度。TUNEL法观察脾脏组织凋亡情况。免疫组化和Western blot检测脾组织TLR4水平。Western blot检测脾组织MyD88、p38、磷酸化p38 （pp38）、干扰素调节因子3 （IRF3）和bcl -2相关X蛋白（Bax）水平。我们还观察了雄性ApoE（-/-）小鼠在脂多糖（LPS）作用4周后血清自身抗体、脾脏重量、脾细胞凋亡及脾组织中TLR4、MyD88、pp38、IRF3和Bax表达的变化。toll样受体4配体，给药。与B6小鼠相比，ApoE（-/-）小鼠脾肿大，血清IgG水平、ANA和抗dsdna抗体滴度显著升高。ApoE（-/-）组脾细胞凋亡及脾组织中TLR4、MyD88、pp38、IRF3、Bax的表达明显低于B6小鼠。在ApoE（-/-）脾脏组织中，TLR4、MyD88、IRF3、pp38和Bax的表达存在性别差异。LPS诱导TLR4信号分子下调，导致Bax表达降低，血清ANA和抗dsdna抗体滴度升高。因此，TLR4信号通路可能参与维持ApoE（-/-）小鼠脾细胞凋亡和自身抗体产生的平衡。(C) 2012爱思唯尔公司版权所有。
Apolipoprotein E-knockout (ApoE(-/-)) mice, atherosclerosis-prone mice, show an autoimmune response, but the pathogenesis is not fully understood. We investigated the pathogenesis in female and male ApoE(-/-) mice. The spleens of all ApoE(-/-) and C57BL/6 (B6) mice were weighed. The serum IgG level and titers of anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody were assayed by ELISA. Apoptosis of spleen tissue was evaluated by TUNEL. TLR4 level in spleen tissue was tested by immunohistochemistry and Western blot analysis. Levels of MyD88, p38, phosphorylated p38 (pp38), interferon regulatory factor 3 (IRF3) and Bcl-2-associated X protein (Bax) in spleen tissue were detected by Western blot analysis. We also survey the changes of serum autoantibodies, spleen weight, splenocyte apoptosis and the expressions of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue in male ApoE(-/-) mice after 4 weeks of lipopolysaccharide (LPS). Toll-like receptor 4 ligand, administration. ApoE(-/-) mice showed splenomegaly and significantly increased serum level of IgG and titers of ANA and anti-dsDNA antibody as compared with B6 mice. Splenocyte apoptosis and the expression of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue were significantly lower in ApoE(-/-) than B6 mice. The expression of TLR4, MyD88, IRF3, pp38, and Bax differed by sex in ApoE(-/-) spleen tissue. The down-regulation of TLR4 signal molecules induced by LPS led to decreased expression of Bax and increased serum titers of ANA and anti-dsDNA antibody. Therefore, the TLR4 signal pathway may participate in maintaining the balance of splenocyte apoptosis and autoantibody production in ApoE(-/-) mice. (C) 2012 Elsevier Inc. All rights reserved.