The involvement of interleukin-22 in the expression of pancreatic beta cell regenerative Reg genes

Thomas Hill; Olga Krougly; Enayat Nikoopour; Stacey Bellemore; Edwin Lee-Chan; Lynette A Fouser; David J Hill; Bhagirath Singh

doi:10.1186/2045-9769-2-2

Cell Regeneration (Jan 2013)

The involvement of interleukin-22 in the expression of pancreatic beta cell regenerative Reg genes

Thomas Hill,
Olga Krougly,
Enayat Nikoopour,
Stacey Bellemore,
Edwin Lee-Chan,
Lynette A Fouser,
David J Hill,
Bhagirath Singh

Affiliations

Thomas Hill: Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada
Olga Krougly: Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada
Enayat Nikoopour: Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada
Stacey Bellemore: Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada
Edwin Lee-Chan: Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada
Lynette A Fouser: Inflammation and Immunology, Biotherapeutics Research and Development, Pfizer, Cambridge MA 02140, USA
David J Hill: Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada
Bhagirath Singh: Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada

DOI: https://doi.org/10.1186/2045-9769-2-2
Journal volume & issue: Vol. 2, no. 1

Abstract

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Background: In Type 1 diabetes, the insulin-producing β-cells within the pancreatic islets of Langerhans are destroyed. We showed previously that immunotherapy with Bacillus Calmette-Guerin (BCG) or complete Freund's adjuvant (CFA) of non-obese diabetic (NOD) mice can prevent disease process and pancreatic β-cell loss. This was associated with increased islet Regenerating (Reg) genes expression, and elevated IL-22-producing Th17 T-cells in the pancreas. Results: We hypothesized that IL-22 was responsible for the increased Reg gene expression in the pancreas. We therefore quantified the Reg1, Reg2, and Reg 3δ (INGAP) mRNA expression in isolated pre-diabetic NOD islets treated with IL-22. We measured IL-22, and IL-22 receptor(R)- α mRNA expression in the pancreas and spleen of pre-diabetic and diabetic NOD mice. Our results showed: 1) Reg1 and Reg2 mRNA abundance to be significantly increased in IL-22-treated islets in vitro; 2) IL-22 mRNA expression in the pre-diabetic mouse pancreas increased with time following CFA treatment; 3) a reduced expression of IL-22R α following CFA treatment; 4) a down-regulation in Reg1 and Reg 2 mRNA expression in the pancreas of pre-diabetic mice injected with an IL-22 neutralizing antibody; and 5) an increased islet β-cell DNA synthesis in vitro in the presence of IL-22. Conclusions: We conclude that IL-22 may contribute to the regeneration of β-cells by up-regulating Regenerating Reg1 and Reg2 genes in the islets.

Published in Cell Regeneration

ISSN: 2045-9769 (Online)
Publisher: SpringerOpen
Country of publisher: United Kingdom
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: https://cellregeneration.springeropen.com/

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