| Curcumin inhibits interferon-γ signaling in colonic epithelial cells. | |
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MedLine Citation:
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PMID: 22038826 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Curcumin (diferulolylmethane) is an anti-inflammatory phenolic compound found effective in preclinical models of inflammatory bowel diseases (IBD) and in ulcerative colitis patients. Pharmacokinetics of curcumin and its poor systemic bioavailability suggest that it targets preferentially intestinal epithelial cells. The intestinal epithelium, an essential component of the gut innate defense mechanisms, is profoundly affected by IFN-γ, which can disrupt the epithelial barrier function, prevent epithelial cell migration and wound healing, and prime epithelial cells to express major histocompatibility complex class II (MHC-II) molecules and to serve as nonprofessional antigen-presenting cells. In this report we demonstrate that curcumin inhibits IFN-γ signaling in human and mouse colonocytes. Curcumin inhibited IFN-γ-induced gene transcription, including CII-TA, MHC-II genes (HLA-DRα, HLA-DPα1, HLA-DRβ1), and T cell chemokines (CXCL9, 10, and 11). Acutely, curcumin inhibited Stat1 binding to the GAS cis-element, prevented Stat1 nuclear translocation, and reduced Jak1 phosphorylation and phosphorylation of Stat1 at Tyr(701). Longer exposure to curcumin led to endocytic internalization of IFNγRα followed by lysosomal fusion and degradation. In summary, curcumin acts as an IFN-γ signaling inhibitor in colonocytes with biphasic mechanisms of action, a phenomenon that may partially account for the beneficial effects of curcumin in experimental colitis and in human IBD. |
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Authors:
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Monica T Midura-Kiela; Vijayababu M Radhakrishnan; Claire B Larmonier; Daniel Laubitz; Fayez K Ghishan; Pawel R Kiela |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-10-28 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 302 ISSN: 1522-1547 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2011-12-20 Completed Date: 2012-02-16 Revised Date: 2012-05-23 |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G85-96 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Steele Children's Research Center, Warsaw, Poland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Inflammatory Agents, Non-Steroidal / pharmacology* Cells, Cultured Chemokines / drug effects Colon / drug effects* Curcumin / pharmacology* Humans Interferon-gamma / antagonists & inhibitors* Intestinal Mucosa / drug effects*, immunology Janus Kinase 1 / metabolism Major Histocompatibility Complex Mice Phosphorylation STAT1 Transcription Factor / metabolism Signal Transduction / drug effects* Transcription, Genetic / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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5R01DK067286/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents, Non-Steroidal; 0/Chemokines; 0/Jak1 protein, mouse; 0/STAT1 Transcription Factor; 0/STAT1 protein, human; 0/Stat1 protein, mouse; 458-37-7/Curcumin; 82115-62-6/Interferon-gamma; EC 2.7.1.112/JAK1 protein, human; EC 2.7.10.1/Janus Kinase 1 |
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