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

General

Monocyte chemoattractant protein-1 is expressed in pancreatic islets from prediabetic NOD mice and in interleukin-1 beta-exposed human and rat islet cells.
Authors:	Chen, MC Proost, P Gysemans, C Mathieu, C Eizirik, DL
Citation:	Chen MC, etal., Diabetologia. 2001 Mar;44(3):325-32.
RGD ID:	8549575
Pubmed:	PMID:11317664 (View Abstract at PubMed)
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-1 beta-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-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 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-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 inhibitors 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 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. CONCLUSIONS/INTERPRETATION: In rat and human islet cells MCP-1 mRNA is induced 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 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.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
type 1 diabetes mellitus	onset	ISO	Ccl2 (Mus musculus)	8549575; 8549575	mRNA:increased expression:pancreatic islet (mouse)	RGD
type 1 diabetes mellitus	onset	IEP		8549575	mRNA:increased expression:pancreatic islet (mouse)	RGD

Objects Annotated

Genes (Rattus norvegicus)

Ccl2 (C-C motif chemokine ligand 2)

Genes (Mus musculus)

Ccl2 (C-C motif chemokine ligand 2)

Genes (Homo sapiens)

CCL2 (C-C motif chemokine ligand 2)

Objects referenced in this article

Gene	CCL13	C-C motif chemokine ligand 13	Homo sapiens

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