Functional effects of proinflammatory factors present in Sjögren’s syndrome salivary microenvironment in an in vitro model of human salivary gland

• Published in: Scientific reports Vol. 7; no. 1; pp. 11897 - 12
• Main Authors: Arce-Franco, Mayte, Dominguez-Luis, María, Pec, Martina K., Martínez-Gimeno, Carlos, Miranda, Pablo, Alvarez de la Rosa, Diego, Giraldez, Teresa, García-Verdugo, José María, Machado, José David, Díaz-González, Federico
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.09.2017; Nature Publishing Group
• Subjects: 13/106; 13/21; 14/19; 14/28; 14/63; 38/77; 631/250/127/98; 692/699/249/1313; Amylases - immunology; Biopsy; Calcium; Cell Proliferation; Cells, Cultured; Chemokine CXCL12 - immunology; Chemokines; CXCL12 protein; Cytokines; Epithelial cells; Epithelial Cells - immunology; Epithelial Cells - pathology; Exocrine glands; Humanities and Social Sciences; Humans; IL-1β; Immune response; Inflammation; Interferon; Interferon-gamma - immunology; Interleukin-1beta - immunology; Isoproterenol; Keratin; Microscopy; Morphology; multidisciplinary; Parotid gland; Pathogenesis; Post-transcription; Salivary gland; Salivary Glands - immunology; Salivary Glands - pathology; Science; Science (multidisciplinary); Sjogren's syndrome; Sjogren's Syndrome - immunology; Sjogren's Syndrome - pathology; Transcription; Transforming Growth Factor beta - immunology; Tumor Necrosis Factor-alpha - immunology; Tumor necrosis factor-α; γ-Interferon
• DOI: 10.1038/s41598-017-12282-x
• ISSN: 2045-2322

Primary Sjögren’s syndrome (pSS) is an autoimmune exocrinopathy in which the role that the immune response plays in reducing exocrine gland function, including the glandular microenvironment of cytokines, has not been fully understood. Epithelial cells from biopsies of human parotid gland (HPG) were used to establish a model of human salivary gland in vitro . In this model, the functional consequences of several proinflammatory soluble factors present in the pSS glandular microenvironment were assessed. Stimulation with isoproterenol and calcium produced a significant increase in the basal activity of amylase in the HPG cell supernatants. Under these conditions, the presence of TNF-α and CXCL12 increased amylase mRNA cellular abundance, but reduced the amylase activity in the cell-free supernatant in a dose-dependent manner. IL-1β and IFN-γ, but not TGF-β, also diminished amylase secretion by HPG cells. These results suggest that the glandular microenvironment of cytokine, by acting post-transcriptionally, may be responsible, at least in part, for the reduced exocrine function observed in pSS patients. These data may help to a better understanding of the pathogenesis of SS, which in turn would facilitate the identification of new therapeutic targets for this disorder.