ArticlePloS one2012
Regulation of the CCL2 gene in pancreatic β-cells by IL-1β and glucocorticoids: role of MKP-1.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Multiomics approaches reveal direct NF-κB p65 target genes in pancreatic islets during cytokine exposure and in type 1 diabetes.American journal of physiology. Endocrinology and metabolism · 2026Article
- A bioinformatics analysis of the correlation between hepatic ischemia-reperfusion injury and postoperative cognitive dysfunction.Frontiers in genetics · 2025Article
- Channel Expansion in the Ligand-Binding Domain of the Glucocorticoid Receptor Contributes to the Activity of Highly Potent Glucocorticoid Analogues.Molecules (Basel, Switzerland) · 2024Article
- Comparison of the effects of oxidative and inflammatory stresses on rat chondrocyte senescence.Scientific reports · 2023Article
- ICAM-1 Abundance Is Increased in Pancreatic Islets of Hyperglycemic Female NOD Mice and Is Rapidly Upregulated by NF-κB in Pancreatic β-Cells.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Article
- Potent Anti-Inflammatory, Arylpyrazole-Based Glucocorticoid Receptor Agonists That Do Not Impair Insulin Secretion.ACS medicinal chemistry letters · 2021Article
- Partners in Crime: Beta-Cells and Autoimmune Responses Complicit in Type 1 Diabetes Pathogenesis.Frontiers in immunology · 2021Review
- The Ubiquitin Ligase SIAH2 Negatively Regulates Glucocorticoid Receptor Activity and Abundance.Biomedicines · 2020Article
- Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells.Nature communications · 2020Article
- Microglia-derived IL-1β promotes chemokine expression by Müller cells and RPE in focal retinal degeneration.Molecular neurodegeneration · 2017Article
- Oral Corticosterone Administration Reduces Insulitis but Promotes Insulin Resistance and Hyperglycemia in Male Nonobese Diabetic Mice.The American journal of pathology · 2017Article
- Mildly compromised tetrahydrobiopterin cofactor biosynthesis due to Pts variants leads to unusual body fat distribution and abdominal obesity in mice.Journal of inherited metabolic disease · 2016Article
- Article
- IL-1β reciprocally regulates chemokine and insulin secretion in pancreatic β-cells via NF-κB.American journal of physiology. Endocrinology and metabolism · 2015Article
- Dual-Specificity Phosphatase 1 and Tristetraprolin Cooperate To Regulate Macrophage Responses to Lipopolysaccharide.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- CCL20 is elevated during obesity and differentially regulated by NF-κB subunits in pancreatic β-cells.Biochimica et biophysica acta · 2015Article
- Transcriptional regulation of chemokine genes: a link to pancreatic islet inflammation?Biomolecules · 2015Review
- Thiobenzothiazole-modified Hydrocortisones Display Anti-inflammatory Activity with Reduced Impact on Islet β-Cell Function.The Journal of biological chemistry · 2015Article
- Transcription of the gene encoding TNF-α is increased by IL-1β in rat and human islets and β-cell lines.Molecular immunology · 2014Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 β-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 β-cell lines. We discovered that activation of the CCL2 gene by IL-1β required the p65 subunit of NF-κB and was dependent on genomic response elements located in the -3.6 kb region of the proximal gene promoter. CCL2 gene transcription in response to IL-1β was blocked by pharmacological inhibition of the IKKβ and p38 MAPK pathways. The IL-1β-mediated increase in CCL2 secretion was also impaired by p38 MAPK inhibition and by glucocorticoids. Moreover, multiple synthetic glucocorticoids inhibited the IL-1β-stimulated induction of the CCL2 gene. Induction of the MAP Kinase Phosphatase-1 (MKP-1) gene by glucocorticoids or by adenoviral-mediated overexpression decreased p38 MAPK phosphorylation, which diminished CCL2 gene expression, promoter activity, and release of CCL2 protein. We conclude that glucocorticoid-mediated repression of IL-1β-induced CCL2 gene transcription and protein secretion occurs in part through the upregulation of the MKP-1 gene and subsequent deactivation of the p38 MAPK. Furthermore, the anti-inflammatory actions observed with MKP-1 overexpression were obtained without suppressing glucose-stimulated insulin secretion. Thus, MKP-1 is a possible target for anti-inflammatory therapeutic intervention with preservation of β-cell function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.