Contribution of ductal cells to cytokine responses by human pancreatic islets

In type 1 diabetes, autoimmune destruction of pancreatic beta-cells has bee n attributed to cytokines released from infiltrating immunocytes. Exposure of isolated islets to cytokines leads to nitric oxide (NO) production, whic h can damage beta-cells. Because ductal cells are closets associated ith hu man beta-cells, we examined whether they can contribute to this process. Is olated human ductal cells were cultured for 48 h with various cytokines. Th e combination of interleukin-1 beta (IL-1 beta) plus interferon-gamma (IFN- gamma) increased nitric oxide production 12-fold while stimulating mRNA exp ression of inducible nitric. oxide synthase (iNOS), In this condition, 10-2 0% of cells positive for the cytokeratin-19 duct marker also stained positi ve for iNOS protein, whereas no positive cells were found in control prepar ations. Comparison of the magnitude of iNOS mRNA expression and nitric oxid e production in these cells with that in isolated human islets suggests tha t >50% of total islet nitric oxide production might originate from associat ed ductal cells. It is concluded that ductal cells are a potential sourer? of nitric oxide production in human islets infiltrated by cytokine-releasin g immunocytes.