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Horm Metab Res 2002; 34(1): 7-12
DOI: 10.1055/s-2002-19959
Original Basic

© Georg Thieme Verlag Stuttgart · New York

Immunoregulation During Disease Progression in Prediabetic NOD Mice: Inverse Expression of Arginase and Prostaglandin H Synthase 2 vs. Interleukin-15

H.  Rothe 1, 2 , A.  Hausmann 1 , H.  Kolb 1
  • 1Germany Diabetes Research Institute at the Heinrich Heine University of Düsseldorf, Düsseldorf, Germany
  • 2Institute of Diabetes Research, Munich, Germany
Further Information

Publication History

Received 3 July 2001

Accepted after Revision 19 September 2001

Publication Date:
14 August 2002 (online)

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Abstract

Non-obese diabetic (NOD) mice spontaneously develop insulin dependent diabetes due to autoimmune destruction of β-cells. The progression of insulitis can be accelerated and synchronized in the pancreas by a single injection of 250 mg/kg cyclophosphamide. In this study, we will report on three immune mediators that were not known to be expressed during insulitis until now. Early insulitis in ten-week-old female NOD mice was associated with strong expression of prostaglandin H synthase 2 in the pancreas and of arginase, an antagonist enzyme of the inducible NO synthase. After acceleration of insulitis progression by cyclophosphamide, expression of the two enzymes was downregulated within 24 h. There was strong concomitant upregulation of IL-15 gene expression that preceded lymphocyte invasion of islets and a rise of IFN-γ mRNA levels by several days. The comparison of individual pancreata showed that the expression of IL-12 and IL-18 mRNA closely correlated with levels of IL-15 gene expression. We conclude that arginase and prostaglandin H synthase 2 expression is associated with peri-insulitis, while IL-15 is a candidate cytokine in driving destructive insulitis, as it elicits Th1-cytotoxic responses in lymphoid as well as in non-lymphoid immune cells and is unusually resistant to downregulation by antagonistic cytokines. This is the first report on arginase, prostaglandin H synthase 2 and IL-15 expression in pancreatic lesions of prediabetic NOD mice.

Key words

Non-Obese Diabetic Mice - Insulitis - Cytokines - Innate Immunity - Macrophages - Cyclophosphamide

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Prof. Dr. H. Kolb

German Diabetes Research Institute

Auf'm Hennekamp 65 · 40225 Düsseldorf · Germany

Phone: + 49 (211) 3382 643

Fax: + 49 (211) 3382 606

Email: kolb@ddfi.uni-duesseldorf.de

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