| FOXO1 Increases CCL20 to Promote NF-κB-Dependent Lymphocyte Chemotaxis. | |
| | |
MedLine Citation:
|
PMID: 22240809 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Hepatic insulin resistance (IR) is associated with liver inflammatory diseases, but molecular mechanisms for the association remained elusive. IR is known to increase activity of forkhead box-containing protein O subfamily-1 (FOXO1), a transcription factor that was recently shown to enhance proinflammatory cytokine production in macrophages and adipocytes. Here we report that overexpression of constitutively active FOXO1 markedly increased chemokine ligand 20 (CCL20) expression and secretion in HepG2 hepatoma cells treated with TNF-α. The opposite was seen when endogenous FOXO1 was silenced. FOXO1 did not bind CCL20 promoter directly; instead, it potentiated CCL20 transcription through increasing the binding of p65/p50 heterodimer to a functional nuclear factor-κB site in the human CCL20 promoter. The conditional medium from TNF-α-treated HepG2 cells stimulated migration of human peripheral blood mononuclear cells. This stimulation was significantly enhanced when FOXO1 was overexpressed, and attenuated when FOXO1 was silenced. CCL20 antibody partly blocked the synergistic effect of FOXO1 and TNF-α on peripheral blood mononuclear cells migration. Additionally, TNF-α antagonizes the insulin/Akt signal transduction, thus leading to activation of FOXO1, which is capable of mediating a transcriptional activation role in response to TNF-α on CCL20 gene expression in HepG2 cells and promotes lymphocyte chemotaxis. Furthermore, we found that FOXO1 and CCL20 were coordinately up-regulated in the insulin resistant and inflammatory cell-infiltrated liver of db/db mice, an animal model that displayed hepatic and systemic low-grade inflammation. In conclusion, our data suggest that FOXO1 links IR to lymphocyte chemotaxis in the insulin-resistant hepatocytes and livers by amplifying nuclear factor-κB-dependent hepatic CCL20 production. |
| | |
Authors:
|
Hongming Miao; Yang Zhang; Zhongyan Lu; Liqing Yu; Lixia Gan |
Related Documents
:
|
19435479 - Insights into endocrine-immunological disturbances in autoimmunity and their impact on ... 7160339 - Evidence for cellular mediated immunity in an animal model of autoimmune pituitary dise... 21665879 - Nomilin inhibits metastasis via induction of apoptosis and regulates the activation of ... 22202109 - Antiviral escape strategies developed by bunyaviruses pathogenic for humans. 17127149 - The hypothalamic-pituitary-adrenal axis in critical illness. 12804199 - Biochemical and functional aspects of gonadotrophin-releasing hormone and gonadotrophins. 20943999 - Hydroxylase inhibition abrogates tnf-alpha-induced intestinal epithelial damage by hypo... 18928689 - Immunopathological mechanisms of eosinophilic oesophagitis. 22036759 - Endometrial seedlings. a survival instinct? immunomodulation and its role in the pathop... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-1-12 |
Journal Detail:
|
Title: Molecular endocrinology (Baltimore, Md.) Volume: - ISSN: 1944-9917 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2012-1-13 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8801431 Medline TA: Mol Endocrinol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Biochemistry and Molecular Biology (H.M., Y.Z., Z.L., L.G.), The Third Military Medical University, Chongqing, China, 400038; and Department of Animal and Avian Science (L.Y.), University of Maryland, College Park, Maryland 20742. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: CA-125 can be part of the tumour evaluation criteria in ovarian cancer trials: experience of the GCI...
Next Document: Deletion of CaMKK2 from the Liver Lowers Blood Glucose and Improves Whole-Body Glucose Tolerance in ...