Diabetologia

, Volume 44, Issue 3, pp 325–332 | Cite as

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

  • M.-C. Chen
  • P. Proost
  • C. Gysemans
  • C. Mathieu
  • D. L. Eizirik

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 NG-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

Authors and Affiliations

  • M.-C. Chen
    • 1
  • P. Proost
    • 2
  • C. Gysemans
    • 3
  • C. Mathieu
    • 3
  • D. L. Eizirik
    • 1
  1. 1.Gene Expression Unit, Diabetes Research Center, Vrije Universiteit Brussel, Brussels, BelgiumBE
  2. 2.Laboratory of Molecular Immunology, Rega Institute for Medical Research, Catholic University Louvain, Louvain, BelgiumBE
  3. 3.Laboratory for Experimental Medicine and Endocrinology (LEGENDO), Katholieke Universiteit Leuven, Leuven, BelgiumBE

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