Insulitis, inflammation due to infiltration of immune cells in and around pancreatic islets, is a hallmark of type I diabetes. Different stages of insulitis have been observed in non-obese diabetic (NOD) mice and BioBreeding (BB) rats. Mechanisms involved in the destructive progression of insulitis, however, are not clearly understood. In this study, we examined the role of the cytokine interluekin-1 (IL-1) in stimulating islet cells to produce a chemotactic factor(s) that may play a role in the progression of insulitis. IL-1 induces accumulation of non-=esterified arachidonic acid in islets as demonstrated by isotope dilution mass spectrometry. Some arachidonate metabolites have chemotactic activity. We have observed that conditioned media collected from rat islets treated with 5 units/ml IL-1 contained chemotactic activities for human monocytes determined by modified Boyden chamber assays. The production of chemotactic activity by islets exposed to IL-1 was time-dep endent and completely blocked by treating islets with 1(M actinomycin D. Addition of antiserum raised against rat macrophage chemoattractant protein-1 (MCP-1) to conditioned media significantly inhibited monocyte chemotaxis, suggesting that MCP-1 may, in part, be responsible for the chemotactic activity observed. We confirmed the synthesis of MCP-1 mRNA by rat islets using in situ hybridization. (-cells of the istlet appear to be the source of MCP-1 since primary (-cells and the insulinoma cell line, RINm5F, express MCP-1 mRNA upon IL-1 activation. These results indicate that pancreatic (-cells produce MCP-1 upon IL-1 activation that may play a role in the progression of insulitis associated with autoimmune diabetes.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000954-24
Application #
6336799
Study Section
Project Start
2000-08-01
Project End
2001-07-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
24
Fiscal Year
2000
Total Cost
$6,028
Indirect Cost
Name
Washington University
Department
Type
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Yue, Xuyi; Dhavale, Dhruva D; Li, Junfeng et al. (2018) Design, synthesis, and in vitro evaluation of quinolinyl analogues for ?-synuclein aggregation. Bioorg Med Chem Lett 28:1011-1019
Cade, W Todd; Levy, Philip T; Tinius, Rachel A et al. (2017) Markers of maternal and infant metabolism are associated with ventricular dysfunction in infants of obese women with type 2 diabetes. Pediatr Res 82:768-775
Lucey, Brendan P; Mawuenyega, Kwasi G; Patterson, Bruce W et al. (2017) Associations Between ?-Amyloid Kinetics and the ?-Amyloid Diurnal Pattern in the Central Nervous System. JAMA Neurol 74:207-215
Ohlemacher, Shannon I; Giblin, Daryl E; d'Avignon, D André et al. (2017) Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria. J Clin Invest 127:4018-4030
Lin, Xiaobo; Racette, Susan B; Ma, Lina et al. (2017) Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans. Arterioscler Thromb Vasc Biol 37:2364-2369
Ovod, Vitaliy; Ramsey, Kara N; Mawuenyega, Kwasi G et al. (2017) Amyloid ? concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement 13:841-849
Wei, Xiaochao; Song, Haowei; Yin, Li et al. (2016) Fatty acid synthesis configures the plasma membrane for inflammation in diabetes. Nature 539:294-298
Shields-Cutler, Robin R; Crowley, Jan R; Miller, Connelly D et al. (2016) Human Metabolome-derived Cofactors Are Required for the Antibacterial Activity of Siderocalin in Urine. J Biol Chem 291:25901-25910
Mertins, Philipp; Mani, D R; Ruggles, Kelly V et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534:55-62
Murata, Takahiro; Dietrich, Hans H; Horiuchi, Tetsuyoshi et al. (2016) Mechanisms of magnesium-induced vasodilation in cerebral penetrating arterioles. Neurosci Res 107:57-62

Showing the most recent 10 out of 696 publications