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

被引:129
作者
Chen, MC
Proost, P
Gysemans, C
Mathieu, C
Eizirik, DL
机构
[1] Free Univ Brussels, Ctr Diabet Res, Gene Express Unit, B-1090 Brussels, Belgium
[2] Katholieke Univ Leuven, Rega Inst Med Res, Lab Mol Immunol, B-3000 Louvain, Belgium
[3] Katholieke Univ Leuven, LEGENDO, Lab Expt Med & Endocrinol, Louvain, Belgium
关键词
beta cell; MCP-1; interleukin-1; nitric oxide; diabetes mellitus; NOD mice; pancreatic islets; interferon-gamma; human islets; polymerase chain reaction;
D O I
10.1007/s001250051622
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. Conclusion/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.
引用
收藏
页码:325 / 332
页数:8
相关论文
共 56 条
  • [31] Prolonged exposure of human beta cells to elevated glucose levels results in sustained cellular activation leading to a loss of glucose regulation
    Ling, ZD
    Pipeleers, DG
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1996, 98 (12) : 2805 - 2812
  • [32] Role of MCP-1 and RANTES in inflammation and progression to fibrosis during murine crescentic nephritis
    Lloyd, CM
    Dorf, ME
    Proudfoot, A
    Salant, DJ
    GutierrezRamos, JC
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 1997, 62 (05) : 676 - 680
  • [33] The role of interleukin-1 in the pathogenesis of IDDM
    MandrupPoulsen, T
    [J]. DIABETOLOGIA, 1996, 39 (09) : 1005 - 1029
  • [34] Cytokine induction of monocyte chemoattractant protein-1 gene expression in human endothelial cells depends on the cooperative action of NF-kappa B and AP-1
    Martin, T
    Cardarelli, PM
    Parry, GCN
    Felts, KA
    Cobb, RR
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (05) : 1091 - 1097
  • [35] MATHIESON K, 1994, DATA BASE, V25, P37, DOI 10.1145/190743.190746
  • [36] 1,25-DIHYDROXYVITAMIN-D3 PREVENTS INSULITIS IN NOD MICE
    MATHIEU, C
    LAUREYS, J
    SOBIS, H
    VANDEPUTTE, M
    WAER, M
    BOUILLON, R
    [J]. DIABETES, 1992, 41 (11) : 1491 - 1495
  • [37] PREVENTION OF TYPE-I DIABETES IN NOD MICE BY NONHYPERCALCEMIC DOSES OF A NEW STRUCTURAL ANALOG OF 1,25-DIHYDROXYVITAMIN D-3, KH1060
    MATHIEU, C
    WAER, M
    CASTEELS, K
    LAUREYS, J
    BOUILLON, R
    [J]. ENDOCRINOLOGY, 1995, 136 (03) : 866 - 872
  • [38] Quantification of murine cytokine mRNAs using real time quantitative Reverse Transcriptase PCR
    Overbergh, L
    Valckx, D
    Waer, M
    Mathieu, C
    [J]. CYTOKINE, 1999, 11 (04) : 305 - 312
  • [39] INHIBITION OF MAP KINASE KINASE BLOCKS THE DIFFERENTIATION OF PC-12 CELLS INDUCED BY NERVE GROWTH-FACTOR
    PANG, L
    SAWADA, T
    DECKER, SJ
    SALTIEL, AR
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (23) : 13585 - 13588
  • [40] Pavlovic D, 2000, EUR CYTOKINE NETW, V11, P267