The effect of prolactin over-expression on secretory function in rabbit lacrimal acinar cells

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Lymphocytic infiltration leads to degradation of lacrimal gland extracellular matrix structures in NOD mice exhibiting a Sjögren's syndrome-like exocrinopathy

We previously reported that lacrimal glands (LGs) of male non-obese diabetic (NOD) mice, an established mouse model of autoimmune inflammatory LG disease that displays many features of human LGs in patients afflicted with Sjögren's syndrome (SjS), exhibit significant degradation of extracellular matrix (ECM) structures as well as increased expression of matrix metalloproteinases (MMPs). The purpose of the current study was to expand the spectrum of proteases identified, to clarify their probable origin as well as to identify the contribution of these changes to disease pathogenesis. We explored in depth the changes in ECM structures and ECM protease expression at the onset of disease (6 weeks) versus late stage disease (18 weeks) in male NOD mouse LGs, relative to LGs of age-matched male NODscid, a severely immunocompromised congenic strain, and healthy BALB/c mice. LG tissues were examined using routine histological, immunohistochemical, Western Blot and gene expression analyses novel multiphoton imaging technologies. We further characterized the profile of infiltrating immune cells under each condition using flow cytometry. Our results show that the initial infiltrating cells at 6 weeks of age are responsible for increased MMP and cathepsin H expression and therefore initiate the LG ECM degradation in NOD mice. More importantly, NODscid mice exhibited normal LG ECM structures, indicating the lymphocytes seen in the LGs of NOD mice are responsible for the degradation of the LG ECM. The disease-related remodeling of LG ECM structures may play a crucial role in altering the acinar signaling environment, disrupting the signaling scaffolds within the cells, which are required to mobilize the exocytotic trafficking machinery, ultimately leading to a loss of LG function in patients afflicted with SjS

Effect of microcystin-LR on protein phosphatase 2A and its function in human amniotic epithelial cells*

Due to their toxicity, the increased distribution of microcystins (MCs) has become an important worldwide problem. MCs have been recognized as inhibitors of protein phosphatase 2A (PP2A) through their binding to the PP2A catalytic subunit. However, the exact mechanism of MC toxicity has not been elucidated, especially concerning the cellular response and its autoregulation. To further dissect the role of PP2A in MC-induced toxicity, the present study was undertaken to determine the response of PP2A in human amniotic epithelial (FL) cells treated with microcystin-LR (MCLR), one of the MC congeners. The results show that a low-dose treatment of MCLR in FL cells for 6 h induced an increase in PP2A activity, and a high-dose treatment of MCLR for 24 h decreased the activity of PP2A, as expected. The increased mRNA and protein levels of the PP2A C subunit may explain the increased activity of PP2A. Furthermore, MCLR altered microtubule post-translational modifications through PP2A. These results further clarify the underlying mechanism how MCLR affects PP2A and may be helpful for elucidating the complex toxicity of MCLR