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

Authors

Bhagirath Singh
Thomas Hill
Olga Krougly, University of Western Ontario
Enayat Nikoopour, University of Western Ontario
Stacey Bellemore, University of Western Ontario
Edwin Lee-Chan, University of Western Ontario
Lynette A. Fouser, Pfizer Inc
David J. Hill, Lawson Health Research Institute, University of Western Ontario

Document Type

Article

Publication Date

4-4-2013

Journal

Cell Regeneration

Volume

2

Issue

2

First Page

1

Last Page

8

URL with Digital Object Identifier

http://www.cellregenerationjournal.com/content/2/1/2

Abstract

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 Reg3δ (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-22Rα following CFA treatment; 4) a down-regulation in Reg1 and Reg2 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.

Notes

doi:10.1186/2045-9769-2-2

Citation of this paper:

Hill T, Krougly O, Nikoopour E, Bellemore S, Lee-Chan E, Fouser LA, Hill DJ and Singh B. The involvement of Interleukin-22 in the expression of Pancreatic Beta cell Regenerating REG genes. Cell Regeneration. 2013; 2(2):1-8