PMID- 11317664
OWN - NLM
STAT- MEDLINE
DCOM- 20010823
LR  - 20190816
IS  - 0012-186X (Print)
IS  - 0012-186X (Linking)
VI  - 44
IP  - 3
DP  - 2001 Mar
TI  - Monocyte chemoattractant protein-1 is expressed in pancreatic islets from 
      prediabetic NOD mice and in interleukin-1 beta-exposed human and rat islet cells.
PG  - 325-32
AB  - 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.
FAU - Chen, M C
AU  - Chen MC
AD  - Gene Expression Unit, Diabetes Research Center, Vrije Universiteit Brussel, 
      Laarbeeklaan 103, B-1090 Brussels, Belgium.
FAU - Proost, P
AU  - Proost P
FAU - Gysemans, C
AU  - Gysemans C
FAU - Mathieu, C
AU  - Mathieu C
FAU - Eizirik, D L
AU  - Eizirik DL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 27JT06E6GR (omega-N-Methylarginine)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - TBT296U68M (1-Methyl-3-isobutylxanthine)
SB  - IM
MH  - 1-Methyl-3-isobutylxanthine/pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/*genetics
MH  - Diabetes Mellitus, Type 1/genetics/*immunology
MH  - Female
MH  - Flow Cytometry
MH  - Gene Expression Regulation/drug effects/*immunology
MH  - Humans
MH  - Interferon-gamma/pharmacology
MH  - Interleukin-1/*pharmacology
MH  - Islets of Langerhans/drug effects/*immunology/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Prediabetic State/genetics/*immunology
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - Rats, Wistar
MH  - Recombinant Proteins/pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Time Factors
MH  - Transcription, Genetic/drug effects/*immunology
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - omega-N-Methylarginine/pharmacology
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2001/04/25 10:00
MHDA- 2001/08/24 10:01
CRDT- 2001/04/25 10:00
PHST- 2001/04/25 10:00 [pubmed]
PHST- 2001/08/24 10:01 [medline]
PHST- 2001/04/25 10:00 [entrez]
AID - 10.1007/s001250051622 [doi]
PST - ppublish
SO  - Diabetologia. 2001 Mar;44(3):325-32. doi: 10.1007/s001250051622.