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Increased expression of cathepsins and obesity-induced proinflammatory cytokines in lacrimal glands of male NOD mouse. | LitMetric

AI Article Synopsis

  • The study focused on the immune cell infiltration and lipid buildup in the lacrimal glands of male NOD mice, a model for Sjögren's syndrome (SjS), by examining gene expression differences compared to healthy mice.
  • Researchers employed microarray analysis and real-time RT-PCR to identify specific upregulated genes, including cathepsins and proinflammatory cytokines, and used immunofluorescence and Western blot techniques to study protein levels and localization.
  • The findings revealed increased activity of cathepsin S and H alongside cytokines, suggesting these could play a role in the autoimmune process of SjS, with cathepsin S levels in tears potentially serving as a diagnostic

Article Abstract

Purpose: Lacrimal glands (LGs) of male NOD mice, a model of Sjögren's syndrome (SjS), exhibit immune cell infiltration and lipid deposition. The mechanism of SjS was further investigated by characterizing gene expression profiles of NOD mouse LGs in comparison with those of healthy control mice. Differentially expressed genes were further investigated at the protein level to correlate changes in location and abundance with development of disease.

Methods: Microarray followed by real-time RT-PCR was conducted to compare the gene expression in 12-week-old male NOD mouse LG relative to that in matched BALB/c mouse LG. Immunofluorescence and Western blot analyses were used to localize and quantify proteins of interest. Enzymatic assays measured catalytic activity of cathepsins.

Results: Cathepsin H (Ctsh), S (Ctss), and Z (Ctsz) and proinflammatory factors, including tumor necrosis factor (Tnf), interleukin 6 (Il6), and interleukin 1 beta (Il1b), were upregulated at the mRNA level. Increased cathepsin S immunofluorescence was detected in lysosomes and secretory vesicle-like organelles in LG acinar cells and CD68-positive infiltrating macrophages in NOD mouse LG. Cathepsin S (CATS) and cathepsin H (CATH) activities were significantly higher in NOD mouse LG lysate than in control lysates, and CATS was also significantly elevated in NOD mouse tears.

Conclusions: Expression of CATS and CATH increases in parallel with proinflammatory cytokines during the development of autoimmune inflammatory disease in the NOD mouse disease model. Tear CATS may represent a biomarker for diagnosis of dacryoadenitis in SjS.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3066616PMC
http://dx.doi.org/10.1167/iovs.09-4523DOI Listing

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