原创力文档regulation of the ccl2 gene in pancreatic β-cells by il-1β and glucocorticoids role of mkp-1ccl2调节基因在胰腺β-cells il-1βmkp-1和糖皮质激素的作用.pdfVIP
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regulation of the ccl2 gene in pancreatic β-cells by il-1β and glucocorticoids role of mkp-1ccl2调节基因在胰腺β-cells il-1βmkp-1和糖皮质激素的作用
Regulation of the CCL2 Gene in Pancreatic b-Cells by IL-
1b and Glucocorticoids: Role of MKP-1
1 1 1 2 3
Susan J. Burke , Matthew R. Goff , Barrett L. Updegraff , Danhong Lu , Patricia L. Brown ,
3 3 1,5 1,4,5 1,5
Steven C. Minkin Jr , John P. Biggerstaff , Ling Zhao , Michael D. Karlstad , J. Jason Collier *
1 Department of Nutrition, University of Tennessee, Knoxville, Tennessee, United States of America, 2 Sarah W. Stedman Nutrition and Metabolism Center, Duke University
Medical Center, Durham, North Carolina, United States of America, 3 Advanced Microscopy and Imaging Center, University of Tennessee, Knoxville, Tennessee, United
States of America, 4 Department of Surgery, Graduate School of Medicine, University of Tennessee Medical Center, Knoxville, Tennessee, United States of America,
5 University of Tennessee Obesity Research Center, Knoxville, Tennessee, United States of America
Abstract
Release of pro-inflammatory cytokines from both resident and invading leukocytes within the pancreatic islets impacts the
development of Type 1 diabetes mellitus. Synthesis and secretion of the chemokine CCL2 from pancreatic b-cells in
response to pro-inflammatory signaling pathways influences immune cell recruitment into the pancreatic islets. Therefore,
we investigated the positive and negative regulatory components controlling expression of the CCL2 gene using isolated
rat islets and INS-1-derived b-cell lines. We discovered that activation of the CCL2 gene by IL-1b required the p65 subunit of
NF-kB and was dependent on genomic resp
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