Diabetologia

, Volume 44, Issue 3, pp 325–332

Monocyte chemoattractant protein-1 is expressed in pancreatic islets from prediabetic NOD mice and in interleukin-1β-exposed human and rat islet cells

Authors

  • M.-C. Chen
    • Gene Expression Unit, Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium
  • P. Proost
    • Laboratory of Molecular Immunology, Rega Institute for Medical Research, Catholic University Louvain, Louvain, Belgium
  • C. Gysemans
    • Laboratory for Experimental Medicine and Endocrinology (LEGENDO), Katholieke Universiteit Leuven, Leuven, Belgium
  • C. Mathieu
    • Laboratory for Experimental Medicine and Endocrinology (LEGENDO), Katholieke Universiteit Leuven, Leuven, Belgium
  • D. L. Eizirik
    • Gene Expression Unit, Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium
Article

DOI: 10.1007/s001250051622

Cite this article as:
Chen, M., Proost, P., Gysemans, C. et al. Diabetologia (2001) 44: 325. doi:10.1007/s001250051622

Abstract

Aims/hypothesis. Monocyte chemoattractant protein-1 (MCP-1) attracts monocytes and T lymphocytes, and could thus contribute to mononuclear cell infiltration in Type I (insulin-dependent) diabetes mellitus. Cytokines induce MCP-1 mRNA expression in pancreatic rat beta cells. To investigate this issue, we analysed the signal transduction for IL-1β-induced MCP-1 expression in rat beta cells and in vitro MCP-1 mRNA expression and protein release by human islets as well as in vivo islet MCP-1 mRNA expression in prediabetic non-obese diabetic mice. Methods. Fluorescence-activated cell sorting-purified rat beta cells were cultured for 6 h with IL-1β (30 U/ml) or MAPK inhibitors or both. Human islets were cultured for 6–72 h with the cytokines IL-1β, IFN-γ or the inducible nitric oxide synthase (iNOS) inhibitor N G-methyl-l-arginine or both. We measured MCP-1 mRNA by RT-PCR and protein by ELISA. The MCP-1 mRNA expression in islets from male and female non-obese diabetic mice (2–12 weeks of age) was measured by real time reverse transcription-polymerase chain reaction (RT-PCR). Results. Interleukin-1β induced MCP-1 mRNA expression in rat beta cells, with a maximum induction after 6 h. A combination of p38 and ERK1/2 inhibitors decreased MCP-1 expression by 70 %. IL-1β induced both MCP-1 mRNA expression and a threefold increase in medium MCP-1 protein accumulation in human islet cells. This effect was not prevented by iNOS blockers. In vivo there was an age-related increase in MCP-1 mRNA expression in islets from male and female non-obese diabetic mice, reaching a peak at 8 weeks. Conclusion/interpretation. In rat and human islet cells MCP-1 mRNA is induced by IL-1β. Both ERK1/2 and p38 MAPK, but not nitric oxide, contribute to MCP-1 expression. In non-obese diabetic mice MCP-1 mRNA expression increases with age, peaking at the early phases of insulitis. The production of MCP-1 by pancreatic beta cells could contribute to the recruitment of mononuclear cells into pancreatic islets in early Type I diabetes. [Diabetologia (2001) 44: 325–332]

Keywords Beta cell MCP-1 interleukin-1 nitric oxide diabetes mellitus NOD mice pancreatic islets interferon-γ human islets polymerase chain reaction.

Copyright information

© Springer-Verlag Berlin Heidelberg 2001