| Tumor necrosis factor (TNF)-alpha-induced IL-8 expression in gastric epithelial cells: role of reactive oxygen species and AP endonuclease-1/redox factor (Ref)-1. | |
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MedLine Citation:
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PMID: 19376732 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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TNF-alpha contributes to oxidative stress via induction of reactive oxygen species (ROS) and pro-inflammatory cytokines. The molecular basis of this is not well understood but it is partly mediated through the inducible expression of IL-8. As redox factor-1 (Ref-1), is an important mediator of redox-regulated gene expression we investigated whether ROS and Ref-1 modulate TNF-alpha-induced IL-8 expression in human gastric epithelial cells. We found that TNF-alpha treatment of AGS cells enhanced nuclear expression of Ref-1 and potently induced IL-8 expression. Overexpression of Ref-1 enhanced IL-8 gene transcription at baseline and after TNF-alpha treatment whereas Ref-1 suppression and antioxidant treatment inhibited TNF-alpha-stimulated IL-8 expression. TNF-alpha-mediated enhancement of other pro-inflammatory chemokines like MIP-3 alpha and Gro-alpha was also regulated by Ref-1. Although TNF-alpha increased DNA binding activity of Ref-1-regulated transcription factors, AP-1 and NF-kappaB, to the IL-8 promoter, promoter activity was mainly mediated by NF-kappaB binding. Silencing of Ref-1 in AGS cells inhibited basal and TNF-alpha-induced AP-1 and NF-kappaB DNA binding activity, but not their nuclear accumulation. Collectively, we provide the first mechanistic evidence of Ref-1 involvement in TNF-alpha-mediated, redox-sensitive induction of IL-8 and other chemokines in human gastric mucosa. This has implications for understanding the pathogenesis of gastrointestinal inflammatory disorders. |
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Authors:
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Ann M O'Hara; Asima Bhattacharyya; Jie Bai; Randy C Mifflin; Peter B Ernst; Sankar Mitra; Sheila E Crowe |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-04-18 |
Journal Detail:
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Title: Cytokine Volume: 46 ISSN: 1096-0023 ISO Abbreviation: Cytokine Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-05-26 Completed Date: 2009-09-07 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 9005353 Medline TA: Cytokine Country: United States |
Other Details:
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Languages: eng Pagination: 359-69 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcysteine
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metabolism Cells, Cultured DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics, metabolism* Epithelial Cells / cytology, metabolism* Free Radical Scavengers / metabolism Gastric Mucosa / cytology*, metabolism Humans Interleukin-8 / genetics, metabolism* Promoter Regions, Genetic Proto-Oncogene Proteins c-fos / genetics, metabolism Proto-Oncogene Proteins c-jun / genetics, metabolism RNA Interference RNA, Small Interfering / genetics, metabolism Reactive Oxygen Species / metabolism* Tumor Necrosis Factor-alpha / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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DK67629/DK/NIDDK NIH HHS; R01 DK061769-07/DK/NIDDK NIH HHS; R01 DK51677/DK/NIDDK NIH HHS; R01 DK61769/DK/NIDDK NIH HHS; R0I ES 08457/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Free Radical Scavengers; 0/Interleukin-8; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Small Interfering; 0/Reactive Oxygen Species; 0/Tumor Necrosis Factor-alpha; 616-91-1/Acetylcysteine; EC 4.2.99.18/APEX1 protein, human; EC 4.2.99.18/DNA-(Apurinic or Apyrimidinic Site) Lyase |
| Comments/Corrections | |
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