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A. Azzarolo, K. Vellala, O. Ponomareva, M. Deighan, V. Seamon; Sjögren’s Syndrome – Genetic Background Enhances Up–Regulation of Ovariectomy–Induced Inflammatory Mediators . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4425.
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Purpose: Sjögren’s syndrome (SS) is characterized by lymphocytic infiltration of the lacrimal glands (LG). The development of lymphocytic infiltrates has been shown to coincide with the overexpression of proinflammatory cytokines in SS patients. 90% of all SS patients are post–menopausal women, however, not all post–menopausal women develop SS. Therefore we hypothesized that a decline in the serum levels of sex hormones promotes a transient inflammatory response in the lacrimal glands, and this response is more pronounced in an appropriate genetic background. Methods: Five wks old C57BL/10SnJ (n=3), control, and NOD.B10–H2b (n=3), mouse model of SS, were ovariectomized (OVX) or sham operated. After 1 week, the lacrimal glands were removed, pooled, total RNA extracted and cDNA gene array analysis was performed for inflammatory cytokines, chemokines. Results: OVX upregulated the expression of inflammatory cytokines, chemokines and their receptors in the LG compared to their respective shams. The number of upregulated inflammatory mediators was greater in the OVX autoimmune predisposed animals compared to the OVX controls. These include IL–1ß, IL–12 RB2, INF–γ, CXCL10, CCR1, TNFα, TNFRSF1α, TNFRSF1ß. A decrease in the expression of the humoral cytokines was also observed in the OVX NOD mice compared to the OVX controls. Conclusions: These results support our hypothesis that reduction of the circulatory levels of sex hormones causes an overexpression of inflammatory mediators in control and NOD animals, and this response was more prominent in the autoimmune predisposed mice. Also, a lack of sex hormones seems to accelerate the development of SS pathology in the genetically predisposed mice.
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