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

Aims/hypothesis. Monocyte chemoattractant protein-1 (MCP-1) attracts monocy tes and T lymphocytes, and could thus contribute to mononuclear cell infilt ration in Type I (insulin-dependent) diabetes mellitus. Cytokines induce MC P-1 mRNA expression in pancreatic rat beta cells. To investigate this issue , we analysed the signal transduction for IL-1 beta -induced MCP-1 expressi on 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 prediabe tic non-obese diabetic mice. Methods. Fluorescence-activated cell sorting-purified rat beta cells were c ultured for 6 h with IL-1 beta (30 U/ml) or MAPK inhibitors or both. Human islets were cultured for 6-72 h with the cytokines IL-1 beta, IFN-gamma or the inducible nitric oxide synthase (iNOS) inhibitor NG;methyl-L-arginine o r both. We measured MCP-1 mRNA by RT-PCR and protein by ELISA. The MCP-1 mR NA expression in islets from male and female non-obese diabetic mice (2-12 weeks of age) was measured by real time reverse transcription-polymerase ch ain reaction (RT-PCR). Results. Interleukin-1 beta induced MCP-1 mRNA expression in rat beta cells , with a maximum induction after 6 h. A combination of p38 and ERK1/2 inhib itors decreased MCP-1 expression by 70 %. IL-1 beta induced both MCP-1 mRNA expression and a threefold increase in medium MCP-1 protein accumulation i n human islet cells. This effect was not prevented by iNOS blockers. In viv o 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 induc ed by IL-1 beta. Both ERK1/2 and p38 MAPK, but not nitric oxide, contribute to MCP-1 expression. In non-obese diabetic mice MCP-1 mRNA expression incr eases with age, peaking at the early phases of insulitis. The production of MCP-1 by pancreatic beta cells could contribute to the recruitment of mono nuclear cells into pancreatic islets in early Type I diabetes.