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-β oestradiol (E2) 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: E2-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 E2 treatments. In addition, enlargement of the spleen (splenomegaly) was also observed in E2-treated mice.
Conclusions: Our results support the hypothesis that oestrogen aggravates severity of the SLE-like symptoms in C4-deficient mice.
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http://dx.doi.org/10.12932/AP0624.33.4.2015 | DOI Listing |
Front Cell Neurosci
May 2023
Department of Biomedical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Complement system plays an important role in the immune defense against pathogens; however, recent studies demonstrated an important role of complement subunits C1q, C4, and C3 in normal functions of the central nervous system (CNS) such as non-functional synapse elimination (synapse pruning), and during various neurologic pathologies. Humans have two forms of C4 protein encoded by C4A and C4B genes that share 99.5% homology, while mice have only one C4B gene that is functionally active in the complement cascade.
View Article and Find Full Text PDFCell Host Microbe
April 2019
Protein and Nucleic Acid Chemistry Division, Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. Electronic address:
The complement system is vital for anti-microbial defense. In the classical pathway, pathogen-bound antibody recruits the C1 complex (C1qC1rC1s) that initiates a cleavage cascade involving C2, C3, C4, and C5 and triggering microbial clearance. We demonstrate a C4-dependent antiviral mechanism that is independent of downstream complement components.
View Article and Find Full Text PDFClin Exp Immunol
February 2018
Program in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Defining how self-antigens are perceived by the immune system is pivotal to understand how tolerance is maintained under homeostatic conditions. Clinically relevant, natural autoantigens targeted by autoantibodies, in e.g.
View Article and Find Full Text PDFArthritis Rheumatol
December 2016
University of Florida, Gainesville.
Objective: In vitro studies suggest that the type I interferon (IFN) signature seen in most lupus patients results from Fcγ receptor-mediated uptake of nucleic acid-containing immune complexes by plasmacytoid dendritic cells and engagement of endosomal Toll-like receptors. The aim of this study was to reexamine the pathogenesis of the IFN signature in vivo.
Methods: Lupus was induced in mice by injecting pristane.
Asian Pac J Allergy Immunol
December 2015
Department of Anatomy, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
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