The Salivary Gland Epithelial Cell in Sjogren's Syndrome: What Are the Steps Involved in Wounding or Killing Their Secretory Function?

The Journal of Rheumatology (Impact Factor: 3.19). 06/2012; 39(6):1117-9. DOI: 10.3899/jrheum.120278
Source: PubMed
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    ABSTRACT: To investigate a possible role of adiponectin in pathogenesis of autoimmune sialoadenitis in non-obese diabetic (NOD) mouse model of Sjögren's syndrome. Expression of adiponectin and its receptors (AdipoR1/2) was detected by PCR, immunoblotting or immunofluorescence. The level of adiponectin was quantified by ELISA. Adiponectin-related signaling molecules and pro-inflammatory cytokines were examined by PCR or immunoblotting. Apoptosis was evaluated by TUNEL staining, flow cytometry, and caspase 3 activation. Adiponectin and AdipoR1/2 mRNA and protein were expressed in submandibular glands. Adiponectin immunostaining was widely diffused in the cytoplasm of acinar and dutal cells. AdipoR1 was mainly distributed in acinar cytoplasm, while AdipoR2 was predominantly located at acinar cell membrane. Submandibular adiponectin levels were reduced during the progression of autoimmune sialoadenitis in 7-, 14-, and 21-week-old NOD mice, while AdipoR1/2 were unchanged. The levels of phosphorylated adenosine monophosphate activated protein kinase, extracellular signal-regulated kinase 1/2, and p38 mitogen-activated protein kinase were decreased, while interferon (IFN)-γ and glandular apoptosis were temporally increased at all time-points. Moreover, exogenous adiponectin supplement inhibited, whereas neutralizing endogenous adiponectin by its antibody promoted, IFN-γ-induced apoptosis and caspase 3 activation in cultured submandibular acinar cells. Adiponectin plays a protective role on submandibular cells. Decreased adiponectin might promote glandular destruction in autoimmune sialoadenitis. This article is protected by copyright. All rights reserved.
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    ABSTRACT: The study of fundamental mechanisms of autoimmunity has been instrumental to clinical progress in the diagnosis and treatment of a range of immune-mediated inflammatory disorders. Dutch immunology has made major contributions to these developments, ranging from fundamental studies on immune cells, antibodies and cytokines to translational and clinical studies with targeted therapies in patients. In this paper we illustrate the progress made in our understanding of autoimmunity and the translational implications for human disease management by focusing on three areas: the autoantibody response in rheumatoid arthritis (RA), T-B cell interactions in Sjögren's syndrome (SS), and cytokine targeting in spondylarthritis (SpA).
    Immunology Letters 10/2014; 162(2). DOI:10.1016/j.imlet.2014.10.013 · 2.51 Impact Factor