Interleukin-17 stimulates inducible nitric oxide synthase-dependent toxicity in mouse beta cells
Аутори:Miljković, Đorđe M.
Cvetković, Ivana D.
Momčilović, Miljana B.
Maksimović-Ivanić, Danijela D.
Stošić-Grujičić, Stanislava D.
Trajković, Vladimir S
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The influence of the proinflammatory cytokine interleukin (IL)-17 on inducible nitric oxide (NO) synthase (iNOS)-mediated NO release was investigated in the mouse insulinoma cell line MIN6 and mouse pancreatic islets. IL-17 markedly augmented iNOS mRNA/protein expression and subsequent NO production induced in MIN6 cells or pancreatic islets by different combinations of interferon-gamma, tumor necrosis factor-alpha, and IL-1 beta. The induction of iNOS by IL-17 was preceded by phosphorylation of p38 mitogen-activated protein kinase (MAPK), and inhibition of p38 MAPK activation completely abolished IL-17-stimulated NO release. IL-17 enhanced the NO-dependent toxicity of proinflammatory cytokines toward MIN6 cells, while IL-17-specific neutralizing antibody partially reduced the NO production and rescued insulinoma cells and pancreatic islets from NO-dependent damage induced by activated T cells. Finally, a significant increase in blood IL-17 levels was observed in a multiple low-dose streptozotocin model of diabetes, suggesting that T cell-derived IL-17 might be involved in NO-dependent damage of beta cells in this disease.
Извор:Cellular and Molecular Life Sciences, 2005, 62, 22, -2668