| Sjögren’s Syndrome (SS) is a chronic, inflammatory autoimmune disease affecting mostly the exocrine cells of lacrimal and salivary glands, leading to diminished secretory function and resulting in keratoconjunctivitis sicca (dry eye disease) and/or stomatitis sicca (dry mouth disease). Despite several decades of studies focusing on autoimmune diseases and dry eye diseases, the exact etiology and mechanisms of SS remain unknown. Besides the fact that SS is often unreported, unrecognized and untreated, today’s therapies rely exclusively on treating the symptoms after disease progression; there exists neither prevention therapy nor cure for SS. In addition, SS has been diagnosed predominantly in post-menopausal women with the female to male ratio reaching 9:1, suggesting a role of ovarian sex hormones in the pathogenesis of SS. However, not all postmenopausal women develop SS, indicating the contribution of other factors such as a genetic background to the onset of SS. In the present study, ovariectomized (OVX) NOD.B10.H2b mice provide a model of menopause with a genetic predisposition to SS, as compared to non-predisposed C57BL/10 mice. Both strands of mice were either sham operated, OVX, OVX and treated with 17β estradiol (E2), or OVX and treated with dihydrotestosterone (DHT). Lacrimal glands were collected 3, 7, 21, and 30 days after surgery and processed for RNA analysis by rt-qPCR and protein assays by ELISA to evaluate cytokine expression and concentrations of IL-1β, TNF-α, IFN-γ, IL-10, and IL-4 on a timeline. Overall, our results showed a significant increase in IL-1β, TNF-α, IL-10, and IL-4 expression and levels in the lacrimal glands of OVX NOD.B10.H2b mice as compared to sham operated animals, and treatment with E2 or DHT at time of OVX prevented the increase in cytokine expression and levels. Except for the expression of IL-1β and IL-4, no significant changes in cytokine expression and levels were observed in the lacrimal glands of C57BL/10 mice for all experimental groups. Both expression and levels of IFN-γ remained undetected in both mouse strains for all experimental groups. From this study, we suggest that cytokines are key players in the pathogenesis of SS, and that the specific time frame of up-regulation of each cytokine is crucial to the understanding of the exact disease mechanism. This study further unravels the SS-mechanism, allowing for possible advancement in hormone replacement therapies and cytokine-directed therapies. |
