Interleukin-17 stimulates inducible nitric oxide synthase-dependent toxicity in mouse beta cells

Cell Mol Life Sci. 2005 Nov;62(22):2658-68. doi: 10.1007/s00018-005-5259-0.


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-1beta. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Survival / physiology
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Insulin-Secreting Cells / enzymology*
  • Interleukin-17 / physiology*
  • Mice
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / physiology
  • Nitric Oxide Synthase Type II / toxicity*
  • Recombinant Proteins / pharmacology
  • T-Lymphocytes / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Interleukin-17
  • Recombinant Proteins
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • p38 Mitogen-Activated Protein Kinases