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S. Mostafa, V. Seamon, A. M. Azzarolo; Apoptosis Correlates With the Upregulation of Cytokines and Chemokines in the Lacrimal Glands of Ovariectomized NOD.B10.H2b Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4172.
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© ARVO (1962-2015); The Authors (2016-present)
One of the main characteristics of Sjogren Syndrome (SS) is lacrimal gland cell death. However, the cause and time course of cell death remains to be elucidated. We have been studying disease progression using ovariectomized (OVX) NOD.B10.H2bmice, as a model of menopause combined with a genetic predisposition to SS. Previously, we have shown an increase in gene expression and levels of inflammatory cytokines and chemokines at 7 days post-OVX, while at 21 days post-OVX only IL-10 was upregulated. In this study we investigated the time course of apoptosis after OVX and whether caspase-3 plays a role in lacrimal epithelial cell death.
Six wks old C57BL/10, control and NOD.B10.H2b mice were ovariectomized or sham operated. After 3, 7& 21 days, the lacrimal glands were removed and stained for cleaved caspase 3 and DNA fragmentation using an ApopTag kit (Chemicon). Quantification of the staining was done using image Pro-plus software.
A significant increase in DNA fragmentation (245±10) and cells staining positively for caspase-3 (86±7.8) was found at 7 days post-OVX in NOD.B10.H2b mice compared to sham operated animals (121±15 and 50±6 respectively)(p < 0.05). However, at 21 days, scores were even greater for both DNA fragmentation (418±12.7) and caspase-3 stained cells (140±14.1) in OVX NOD.B10.H2b mice compared to sham operated animals (88±9 and 43±2.4 respectively)(p <0.05). No significant differences were observed in DNA fragmentation or cleaved caspase-3 staining cells between OVX NOD.B10.H2b and the sham operated group at 3 days. Furthermore, no significant changes were observed between the C57BL/10 sham and OVX at any of the experimental time points studied.
Our results suggest that apoptosis of lacrimal gland cells in OVX NOD.B10.H2bmice occurs in conjunction with the upregulation of proinflammatory cytokines and chemokines. Some of these proinflammatory cytokines or chemokines could play a role in the activation of caspase 3, which in turn could be at least in part responsible for the lacrimal gland cell apoptosis.
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