alexa Functional IL-18 Is produced by primary pancreatic mouse islets and NIT-1 beta cells and participates in the progression towards destructive insulitis.
Immunology

Immunology

International Journal of Inflammation, Cancer and Integrative Therapy

Author(s): Frigerio S, Hollnder GA, Zumsteg U

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Abstract BACKGROUND: Preclinical stages of type 1 diabetes are characterized by infiltrating T cells and by the peri- and intra-islet accumulation of pro-inflammatory mediators, such as IFNgamma. METHODS/RESULTS: Using quantitative PCR we demonstrated that mRNA specific for the IFNgamma-inducing cytokine IL-18 is upregulated in NIT-1 beta cells and intact mouse islets upon exposure to IL-1beta, IFNgamma and TNFalpha. The biological activity of IL-18 was blocked using caspase inhibitors and anti-IL-18 antibodies. Increased IL-18 expression was also detected in islets during advanced stages of insulitis and correlated with elevated transcripts for IFNgamma and for the IL-18 receptor. CONCLUSION: Thus, beta cells produce bioactive IL-18 in the course of insulitis and actively contribute to the exacerbation of inflammation leading to their own demise. Copyright 2002 S. Karger AG, Basel This article was published in Horm Res and referenced in International Journal of Inflammation, Cancer and Integrative Therapy

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