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Expression and secretion of alpha1-proteinase inhibitor are regulated by proinflammatory cytokines in human pancreatic islet cells

Bosco, Domenico ; Meda, Paolo ; Morel, Philippe ; Matthey-Doret, David ; Caille, Dorothée ; Toso, Christian ; Bühler, Leo ; Berney, Thierry

In: Diabetologia, 2005, vol. 48, no. 8, p. 1523-1533

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    Title
    • Expression and secretion of alpha1-proteinase inhibitor are regulated by proinflammatory cytokines in human pancreatic islet cells
    Author
    • Bosco, Domenico. Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland
    • Meda, Paolo. Department of Cell Physiology and Metabolism, School of Medicine, University of Geneva, Geneva, Switzerland
    • Morel, Philippe. Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland
    • Matthey-Doret, David. Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland
    • Caille, Dorothée. Department of Cell Physiology and Metabolism, School of Medicine, University of Geneva, Geneva, Switzerland
    • Toso, Christian. Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland
    • Bühler, Leo. Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland
    • Berney, Thierry. Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Diabetologia, 2005, vol. 48, no. 8, p. 1523-1533. Springer-Verlag; http://www.springer.de
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:313959
    Summary
    Aims/hypothesis: Alpha1-proteinase inhibitor (α1-PI) has been considered a key player in inflammatory processes. In humans, the main production site of α1-PI is the liver, but other tissues, including pancreatic islets, also synthesise this molecule. The aims of this study were to assess the islet cell types that produce α1-PI, to determine whether α1-PI is actually secreted by islet cells, and to assess how its production and/or secretion are regulated. Methods: Expression of α1-PI in human islet cells was assessed by immunofluorescence, electron microscopy and western blotting. Release of α1-PI was analysed by reverse haemolytic plaque assay and ELISA. The effects of cytokines on α1-PI synthesis and secretion were tested. Results: Immunofluorescence showed that alpha and delta cells do express α1-PI, whereas beta cells do not. By electron microscopy, we demonstrated a colocalisation of α1-PI with glucagon and somatostatin within secretory granules. Immunolabelling also revealed localisation of α1-PI within the Golgi apparatus, related vesicles and lysosomal structures. The expression of α1-PI in islet cells was also demonstrated by western blotting and ELISA of protein extracts. ELISA and reverse haemolytic plaque assay showed that α1-PI is secreted into the culture medium. Treatment of islet cells with IL-1β and oncostatin M for 4 days increased the production and release of α1-PI. Conclusions/interpretation: Our results demonstrate that α1-PI is expressed by the alpha and delta cells of human islets, and that proinflammatory cytokines enhance the production and release of this inhibitor