Abstract
Purpose: :
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.
Methods: :
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.
Results: :
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.
Conclusions: :
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.
Keywords: lacrimal gland • cytokines/chemokines