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V. Seamon, H. Quinonez, A. Azzarolo; Ovariectomy Persistently Increases the Gene Expression and Protein Levels of Il-1β, Ifn- and Cxcl13 Over Time. Invest. Ophthalmol. Vis. Sci. 2008;49(13):429.
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© ARVO (1962-2015); The Authors (2016-present)
Sjogren’s syndrome (SS), characterized by lacrimal dysfunction and destruction as well as lymphocytic infiltration, primarily affects post-menopausal women whose levels of sex hormones are significantly decreased. However, not all post-menopausal women develop SS. Therefore, we hypothesized that a decline in the circulating levels of sex hormones in a genetically predisposed murine model of SS, will cause an increase in the gene expression and protein levels of IL-1β, IFN-γ and CXCL13, in the lacrimal glands, which becomes more severe and persistent with time compared to a non-genetically predisposed murine strain.
Six wks old C57BL/10SnJ, control, and NOD.B10-H2b, mouse model of SS, were ovariectomized (OVX) or sham operated. After 3, 7 or 21 days, the lacrimal glands were removed, pooled, and homogenized. Total RNA was used to analyze gene expression levels of IL-1β, IFN-γ and CXCL13. ELISA analysis was used to determine protein concentration of IL-1β, IFN-γ and CXCL13.
Ovariectomized NOD mice showed significant and persistent increases in the gene expression and protein levels of IL-1β, IFN-γ and CXCL13 compared to sham operated animals. No significant changes were seen in the gene expression or protein levels of IL-1β, IFN-γ and CXCL13 between the sham and OVX in C57BL/10SnJ mice at any of the experimental time points.
These results support our hypothesis that reduction of the circulatory levels of sex hormones causes an increase in the expression of IL-1β, IFN-γ and CXCL13 in a genetically predisposed murine model of SS. Since this increase becomes more severe and persistent with time, it is reasonable to assume that sex hormones in addition to a genetic predisposition are necessary factors in the development of SS.
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