Autoimmune hepatitis-like disease in C57BL/6 mice infected with mouse hepatitis virus A59.
Autoimmune hepatitis-like disease in C57BL/6 mice infected with mouse hepatitis virus A59.
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DOI：
10.1016/j.intimp.2011.05.020
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发表时间：
2011-10
影响因子：
5.6
通讯作者：
Retegui LA
中科院分区：
文献类型：
--
作者：
Aparicio JL;Peña C;Retegui LA
小鼠肝炎病毒A59 （MHV A59）诱导对富马酰乙酸水解酶（FAH）的自身抗体（autoAb）， FAH是一种存在于肝脏和肾脏的可溶性胞质酶。这项工作的目的是通过使用外源性佐剂PADRE来放大和多样化局限于FAH的自身免疫反应。因此，我们选择了C57BL/6小鼠，因为这些小鼠对PADRE的反应比其他小鼠品系更好。本研究结果令人惊讶地表明，C57BL/6小鼠出现了自身免疫性肝炎样疾病（AIH）的体征，包括短暂性高γ球蛋白血症、转氨酶升高、针对不同肝脏蛋白的自身抗体和肝细胞浸润，这表明病毒接种可以产生一种新的实验性AIH模型。此外，PADRE可增强MHV效应，延长高γ球蛋白血症的持续时间，增加自身抗体的结合以及肝脏浸润程度。然而，佐剂并没有延长症状的时间。此外，由于血浆尿酸和高迁移率组蛋白1 （HGMB1）浓度在MHV-和/或padre处理的小鼠中增加，这表明这两种警报可能参与了病毒感染和佐剂给药诱导的免疫反应的扩散。小鼠肝炎病毒A59诱导C57BL/6小鼠组织产生自身抗体。外源性佐剂PADRE可增强MHV诱导的自身免疫反应。感染MHV的C57BL/6小鼠出现了自身免疫性肝炎样疾病的症状。
Mouse hepatitis virus A59 (MHV A59) induces autoantibodies (autoAb) to fumarylacetoacetate hydrolase (FAH), a soluble cytosolic enzyme present in the liver and kidneys, in various mouse strains. The aim of this work was to amplify and diversify the autoimmune response restricted to FAH through the use of the exogenous adjuvant called PADRE. Accordingly, C57BL/6 mice were chosen, because these animals respond to PADRE better than other mouse strains. Results presented herein indicate that, surprisingly, C57BL/6 mice developed signs of autoimmune hepatitis-like disease (AIH), including transient hypergammaglobulinemia, elevated transaminases, autoAb directed against different liver proteins and hepatic cellular infiltrates, indicating that a new model of experimental AIH could be generated by a viral inoculation. Furthermore, PADRE administration amplified the MHV effect, extending the duration of hypergammaglobulinemia and increasing the binding of autoAb as well as the degree of hepatic infiltrates. However, the adjuvant did not expand the time of the symptoms. Additionally, since plasmatic uric acid and high-mobility group box protein 1 (HGMB1) concentrations augmented in MHV- and/or PADRE-treated mice, it is suggested that both alarmins were probably involved in the spreading of the immune response induced by the viral infection and the adjuvant administration. ► Mouse hepatitis virus A59 induced autoantibodies to mouse tissues in C57BL/6 mice. ► The exogenous adjuvant PADRE amplified the autoimmune response induced by MHV. ► C57BL/6 mice infected with MHV developed signs of autoimmune hepatitis-like disease.
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影响因子：
5.6
作者：
Aparicio JL;Duhalde-Vega M;Loureiro ME;Retegui LA
通讯作者：
Retegui LA
影响因子：
15.3
作者：
Holdener, Martin;Hintermann, Edith;Bayer, Monika;Rhode, Antje;Rodrigo, Evelyn;Hintereder, Gudrun;Johnson, Eric F.;Gonzalez, Frank J.;Pfeilschifter, Josef;Manns, Michael P.;Herrath, Matthias von G.;Christen, Urs
通讯作者：
Christen, Urs
影响因子：
9.9
作者：
LAVI, E;GILDEN, DH;WEISS, SR
通讯作者：
WEISS, SR
影响因子：
13.5
作者：
Lapierre, P;Djilali-Saiah, I;Alvarez, F
通讯作者：
Alvarez, F
影响因子：
2.3
作者：
Hardtke-Wolenski, Matthias;Jaeckel, Elmar
通讯作者：
Jaeckel, Elmar