Caprylic acid and medium‐chain triglycerides inhibit IL‐8 gene transcription in Caco‐2 cells: comparison with the potent histone deacetylase inhibitor trichostatin A

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Abstract
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. 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‐κB and other transcription factors by electrophoretic mobility shift assay (EMSA), and found that caprylic acid did not modulate their activation. 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. Similar results were observed when cells were precultured with the well‐known potent histone deacetylase inhibitor trichostatin A (TSA). 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. British Journal of Pharmacology (2002) 136, 280–286; doi:10.1038/sj.bjp.0704719