ArticleBiochimica et biophysica acta2015
CCL20 is elevated during obesity and differentially regulated by NF-κB subunits in pancreatic β-cells.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The trial behind it
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- Trial
- SOX30 Facilitates Triple-Negative Breast Cancer Metastasis via TNFR2-NF-κB Signaling and Tumor Microenvironment Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 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
- Reduced peroxisomal function increases insulin secretion, promotes insulin oxidation, and impairs β cell maturity.JCI insight · 2026Article
- Circulating and Urinary CCL20 in Human Kidney Disease.International journal of molecular sciences · 2025Article
- Polymerized laminin-modified microcapsules improve pancreatic islet resilience towards cytokine induced inflammatory stress and lower chemoattractant cytokine secretion.Materials today. Bio · 2025Article
- Injectable, reversibly thermoresponsive captopril-laden hydrogel for the local treatment of sensory loss in diabetic neuropathy.Scientific reports · 2024Article
- Channel Expansion in the Ligand-Binding Domain of the Glucocorticoid Receptor Contributes to the Activity of Highly Potent Glucocorticoid Analogues.Molecules (Basel, Switzerland) · 2024Article
- NOD mice have distinct metabolic and immunologic profiles when compared with genetically similar MHC-matched ICR mice.American journal of physiology. Endocrinology and metabolism · 2023Article
- Neutralizing MIP3The Journal of pharmacology and experimental therapeutics · 2023Article
- Review
- Integrating Common Risk Factors with Polygenic Scores Improves the Prediction of Type 2 Diabetes.International journal of molecular sciences · 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
- Pioglitazone Reverses Markers of Islet Beta-Cell De-Differentiation inBiomedicines · 2021Article
- Identifying molecular insight of synergistic complexities for SARS-CoV-2 infection with pre-existing type 2 diabetes.Computers in biology and medicine · 2021Article
- α-CGRP disrupts amylin fibrillization and regulates insulin secretion: implications on diabetes and migraine.Chemical science · 2021Article
- Beta Cell Physiological Dynamics and Dysfunctional Transitions in Response to Islet Inflammation in Obesity and Diabetes.Metabolites · 2020Review
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Enhanced leukocytic infiltration into pancreatic islets contributes to inflammation-based diminutions in functional β-cell mass. Insulitis (aka islet inflammation), which can be present in both T1DM and T2DM, is one factor influencing pancreatic β-cell death and dysfunction. IL-1β, an inflammatory mediator in both T1DM and T2DM, acutely (within 1h) induced expression of the CCL20 gene in rat and human islets and clonal β-cell lines. Transcriptional induction of CCL20 required the p65 subunit of NF-κB to replace the p50 subunit at two functional κB sites within the CCL20 proximal gene promoter. The NF-κB p50 subunit prevents CCL20 gene expression during unstimulated conditions and overexpression of p50 reduces CCL20, but enhances cyclooxygenase-2 (COX-2), transcript accumulation after exposure to IL-1β. We also identified differential recruitment of specific co-activator molecules to the CCL20 gene promoter, when compared with the CCL2 and COX2 genes, revealing distinct transcriptional requirements for individual NF-κB responsive genes. Moreover, IL-1β, TNF-α and IFN-γ individually increased the expression of CCR6, the receptor for CCL20, on the surface of human neutrophils. We further found that the chemokine CCL20 is elevated in serum from both genetically obese db/db mice and in C57BL6/J mice fed a high-fat diet. Taken together, these results are consistent with a possible activation of the CCL20-CCR6 axis in diseases with inflammatory components. Thus, interfering with this signaling pathway, either at the level of NF-κB-mediated chemokine production, or downstream receptor activation, could be a potential therapeutic target to offset inflammation-associated tissue dysfunction in obesity and diabetes.
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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 OpenQuestion graph.