A role of oestrogen in aggravating SLE-like syndrome in C4-deficient mice

作者：Boonsoongnern Prapassorn; Faisaikarm Tassanee; Sangsuwan Parisatcha; Weerachatyanukul Wattana; Kitiyanant Yindee^*

来源：Asian Pacific Journal of Allergy and Immunology, 2015, 33(4): 339-348.

DOI：10.12932/ap0624.33.4.2015

• C4(-/-) mice
• ovariectomised
• 17-beta oestradiol
• systemic lupus erythematosus
• immune complex
• glomerulonephritis

Background: As one of the epigenetic factors, oestrogen is considered to be a predisposing factor that is associated with a susceptibility to autoimmune disease development in women including systemic lupus erythematosus (SLE). Here, we proposed that oestrogen is also imparted in a post-lupus symptomatic enhancement as studied in the C4-deficient (C4(-/-)) mice model known to develop SLE-like symptoms.
Methods: Fifty-six C4 knockout mice were ovariectomised (OVX) to eliminate the effect of endogenous feminine hormones followed by 17-beta oestradiol (E-2) administration in both dose-and time-dependent manners. Histopathological features of kidneys and spleens were studied by histological and immunofluorescent staining. The relative expression levels of IgG and IgM were measured densitometrically on their immunoreactive bands and the level of IgG-anti-double stranded (ds) DNA was measured by ELISA.
Results: E-2-treated mice displayed a gradual increase in immune complex deposition (both IgG and IgM) in glomeruli and proximal convoluted tubules. An increased reactivity of autoantibodies against dsDNA correlated with increasing doses and longer exposure to E-2 treatments. In addition, enlargement of the spleen (splenomegaly) was also observed in E-2-treated mice.
Conclusions: Our results support the hypothesis that oestrogen aggravates severity of the SLE-like symptoms in C4-deficient mice.

• 出版日期2015-12