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Publication : Interleukin 12 mRNA expression in islets correlates with beta-cell destruction in NOD mice.

First Author  Rabinovitch A Year  1996
Journal  J Autoimmun Volume  9
Issue  5 Pages  645-51
PubMed ID  8933280 Mgi Jnum  J:37037
Mgi Id  MGI:84443 Doi  10.1006/jaut.1996.0084
Citation  Rabinovitch A, et al. (1996) Interleukin 12 mRNA expression in islets correlates with beta-cell destruction in NOD mice. J Autoimmun 9(5):645-51
abstractText  Interferon-gamma (IFN-gamma) is implicated as a mediator of islet beta-cell destruction in autoimmune, insulin-dependent diabetes mellitus (IDDM). Because interleukin 12 (IL-12) is a potent inducer of IFN-gamma production, we sought evidence implicating IL-12 in IDDM development. In the present study, we used a reverse transcriptase polymerase chain reaction (RT-PCR) assay to measure IL-12 mRNA expression levels in islets from nonobese diabetic (NOD) mice. Expression of mRNA encoding the p40 chain of IL-12 (IL-12 p40) in mono-nuclear leukocytes isolated from islets of female NOD mice increased progressively from age 5 weeks to diabetes onset (> 13 weeks). By contrast, IL-12 p40 mRNA levels were significantly decreased in islet mononuclear leukocytes, but not spleens, from female NOD mice protected from diabetes by administration of complete Freund's adjuvant (CFA) in early life. In addition, mRNA levels of IL-12 p40, IFN-gamma and IL-2 were significantly decreased in syngeneic islet grafts, but not spleens, from female NOD mice protected from diabetes recurrence by CFA administration at the time of islet transplantation. These findings show that IL-12 gene expression in the insulitis lesion correlates with both primary and recurrent diabetes development in NOD mice, possibly via induction of T helper (Th) 1-type cytokines, IL-2 and IFN-gamma.
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