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Diabetologia. 2005 Aug;48(8):1523-33. Epub 2005 Jul 7.

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

Author information

1
Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, Switzerland. domenico.bosco@medecine.unige.ch

Abstract

AIMS/HYPOTHESIS:

Alpha1-proteinase inhibitor (alpha1-PI) has been considered a key player in inflammatory processes. In humans, the main production site of alpha1-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 alpha1-PI, to determine whether alpha1-PI is actually secreted by islet cells, and to assess how its production and/or secretion are regulated.

METHODS:

Expression of alpha1-PI in human islet cells was assessed by immunofluorescence, electron microscopy and western blotting. Release of alpha1-PI was analysed by reverse haemolytic plaque assay and ELISA. The effects of cytokines on alpha1-PI synthesis and secretion were tested.

RESULTS:

Immunofluorescence showed that alpha and delta cells do express alpha1-PI, whereas beta cells do not. By electron microscopy, we demonstrated a colocalisation of alpha1-PI with glucagon and somatostatin within secretory granules. Immunolabelling also revealed localisation of alpha1-PI within the Golgi apparatus, related vesicles and lysosomal structures. The expression of alpha1-PI in islet cells was also demonstrated by western blotting and ELISA of protein extracts. ELISA and reverse haemolytic plaque assay showed that alpha1-PI is secreted into the culture medium. Treatment of islet cells with IL-1beta and oncostatin M for 4 days increased the production and release of alpha1-PI.

CONCLUSIONS/INTERPRETATION:

Our results demonstrate that alpha1-PI is expressed by the alpha and delta cells of human islets, and that proinflammatory cytokines enhance the production and release of this inhibitor.

PMID:
16001235
DOI:
10.1007/s00125-005-1816-1
[Indexed for MEDLINE]

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