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TY Fields, I Tamba, DJ Bennett, MA Meneray; Gq is Down Regulated in Lacrimal Glands of Pre-Autoimmune NOD and NZB/NZW F1 Mouse Models of Sjogren's Syndrome . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3128.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Recent evidence suggests that intrinsic failures of acinar epithelial cells may initiate the lymphocytic infiltration that is characteristic of Sjogren’s Syndrome (SS). To test this hypothesis, we evaluated in vitro lacrimal acinar secretion and G protein profiles in pre-autoimmune NOD and NZB/NZW F1 female mice. Methods: Lacrimal tissues were obtained for histology from BALB/c (control), NOD and NZB/NZW F1 female mice at 4 to 28 weeks of age. Lymphocytic infiltration of the lacrimal glands was assessed by hematoxylin and eosin staining of paraffin sections. Primary cultures of mouse lacrimal acini were isolated from mice of each strain at 4 and 12 weeks. After 3-4 days in culture, acini were exposed to vehicle, 100µM of carbachol ± 10µM d-ala2-met-enkephalinamide (DALA), 100µM isoproterenol or 100nM vasoactive intestinal peptide (VIP) and secreted protein was measured. Western blotting and RT-PCR were used to determine protein and mRNA expression of the alpha subunits of Gs, Gq, G11, Gi1, Gi2 and Gi3 in 4 and 12 week pre-autoimmune mice. Results: Lymphocytic infiltration was detected at 20 weeks in NOD and at 28 weeks in NZB/NZW F1 mice (n=3). Secretion data showed no significant differences between strains (n=4-9). There was a decrease in the expression of Gqα protein in NOD and NZB/NZW F1 mice compared to controls at both 4 and 12 weeks, but no differences in the other Gα proteins (n=6-9). Correspondingly, RT-PCR showed decreased mRNA expression of Gqα at 4 and 12 weeks. No differences were detected in the mRNA expression for the other Gα proteins (n=6-9). The down regulation of Gqα was more pronounced in NOD than in NZB/NZW F1 mice at both ages. Conclusion:These results indicate alteration of Gqα prior to the onset of autoimmune disease in NOD and NZB/NZW F1 mice. We suggest that an early disruption of G protein signaling pathways may contribute to the development of the autoimmune state in SS. Potential G protein dependent lacrimal processes to be investigated include intracellular trafficking and upregulation of proapoptotic factors by protein kinases.
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