Document Detail


Caprylic acid and medium-chain triglycerides inhibit IL-8 gene transcription in Caco-2 cells: comparison with the potent histone deacetylase inhibitor trichostatin A.
MedLine Citation:
PMID:  12010777     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Medium-chain triglyceride (MCT) is often administered to patients with Crohn's disease (CD) or short-bowel syndrome. However, little is known about the effects of medium-chain fatty acids (MCFAs) and MCT on intestinal inflammation. In this study we examined whether caprylic acid, one of the MCFAs, and MCT suppress IL-8 secretion by differentiated Caco-2 cells. 2. We found for the first time that caprylic acid and MCT suppress IL-8 secretion by Caco-2 cells at the transcriptional level when precultured together for 24 h. We also tried to clarify the mechanism of IL-8 gene inhibition by examining the activation of NF-kappaB and other transcription factors by electrophoretic mobility shift assay (EMSA), and found that caprylic acid did not modulate their activation. 3. The result of dual-luciferase assay using Caco-2 cells transfected with IL-8 promoter/luciferase reporter plasmid revealed that caprylic acid inhibited the activation of IL-8 promoter. 4. Similar results were observed when cells were precultured with the well-known potent histone deacetylase inhibitor trichostatin A (TSA). 5. We examined the state of H4 acetylation in IL-8 promoter using the technique known as chromatin immunoprecipitation (Chr-IP). TSA rapidly induced H4 acetylation in IL-8 promoter chromatin, whereas caprylic acid did not. These results suggest that the inhibition of IL-8 gene transcription induced by caprylic acid and TSA does not necessarily require the marked suppression of transcription factors, and the mechanism of inhibition of IL-8 gene transcription may be different between caprylic acid and TSA.
Authors:
Aihiro Hoshimoto; Yasuo Suzuki; Tatsuro Katsuno; Hiroshi Nakajima; Yasushi Saito
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  136     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-05-15     Completed Date:  2002-10-29     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  280-6     Citation Subset:  IM    
Affiliation:
Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chiba, Japan. Hossy@intmed02.m.chiba-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Caco-2 Cells
Caprylates / pharmacology*
Enzyme Inhibitors / pharmacology
Histone Deacetylase Inhibitors*
Histone Deacetylases / metabolism
Humans
Hydroxamic Acids / pharmacology*
Interleukin-8 / antagonists & inhibitors*,  biosynthesis,  genetics*
Transcription, Genetic / drug effects*,  physiology
Triglycerides / pharmacology*
Chemical
Reg. No./Substance:
0/Caprylates; 0/Enzyme Inhibitors; 0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/Interleukin-8; 0/Triglycerides; 124-07-2/octanoic acid; 3X2S926L3Z/trichostatin A; EC 3.5.1.98/Histone Deacetylases
Comments/Corrections

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