1. Longitudinal analysis of tear cathepsin S activity levels in male non-obese diabetic mice suggests its potential as an early stage biomarker of Sjögren's Syndrome.
- Author
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Janga, Srikanth R., Shah, Mihir, Ju, Yaping, Meng, Zhen, Edman, Maria C., and Hamm-Alvarez, Sarah F.
- Subjects
CATHEPSINS ,SJOGREN'S syndrome ,AUTOIMMUNE diseases ,GENE expression ,CYTOKINES ,IMMUNOFLUORESCENCE - Abstract
Context: Cathepsin S (CTSS) activity is elevated in Sjögren's Syndrome (SS) patient tears. Objective: To evaluate longitudinal expression of tear and tissue CTSS activity relative to other disease indicators in Non-Obese Diabetic (NOD) mice. Methods: CTSS activity was measured in tears and lacrimal glands (LG) from male 1–6 month (M) NOD and 1 and 6 M BALB/c mice. Lymphocytic infiltration was quantified by histopathology, while disease-related proteins (Rab3D, CTSS, collagen 1) were quantified using q-PCR and immunofluorescence. Results: In NOD LG, lymphocytic infiltration was noted by 2 M and established by 3 M (p < 0.01). IFN-ɣ, TNF-α, and MHC II expression were increased by 2 M (p < 0.01). Tear CTSS activity was significantly elevated at 2 M (p < 0.001) to a maximum of 10.1-fold by 6 M (p < 0.001). CTSS activity in LG lysates was significantly elevated by 2 M (p < 0.001) to a maximum of 14-fold by 3 M (p < 0.001). CTSS and Rab3D immunofluorescence were significantly increased and decreased maximally in LG acini by 3 M and 2 M, respectively. Comparable changes were not detected between 1 and 6 M BALB/c mouse LG, although Collagen 1 was decreased by 6 M in LG of both strains. Conclusion: Tear CTSS activity is elevated with other early disease indicators, suggesting potential as an early stage biomarker for SS. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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