期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 136, 期 2, 页码 280-286出版社
WILEY
DOI: 10.1038/sj.bjp.0704719
关键词
Caco-2 cell; caprylic acid; IL-8; MCT; NF-kappa B; transcription; trichostatin A; chromatin immunoprecipitation; histone acetylation
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 It. 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 riot 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.
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