Interleukin-17 stimulates inducible nitric oxide synthase-dependent toxicity in mouse beta cells
2005
Аутори:
Miljković, ĐorđeStojanović, Ivana D.
Momčilović, Miljana
Maksimović-Ivanić, Danijela
Stošić-Grujičić, Stanislava
Trajković, Vladimir S
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2005, Birkhäuser Verlag, Basel
Метаподаци
Приказ свих података о документуАпстракт:
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-
DOI: 10.1007/s00018-005-5259-0
ISSN: 1420-682X