Butyrate blocks interferon-γ-inducible protein-10 release in human intestinal subepithelial myofibroblasts

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Abstract
Interferon (IFN)-γ-inducible protein (IP)-10 is a chemoattractant for CXCR 3-expressing T lymphocytes and monocytes. IP-10 has been reported to mediate chronic inflammation such as that in inflammatory bowel disease (IBD). However, the local secretion of IP-10 in the intestine remains unclear. In this study, we investigated IP-10 secretion in human colonic subepithelial myofibroblasts (SEMFs). IP-10 secretion was determined by enzyme-linked immunosorbent assay (ELISA), and IP-10 mRNA expression was evaluated by Northern blotting. Interleukin (IL)-10 mRNA was not detected in unstimulated SEMFs. Interferon (IFN)-γ strongly induced IP-10 mRNA expression. Tumor necrosis factor (TNF)-α also stimulated IP-10 mRNA expression, but this was much weaker than that induced by IFN-γ. The effects of IFN-γ and TNF-α were detected in a dose- and time-dependent manner. These responses were also observed at the protein levels. The IFN-γ-induced IP-10 secretion was not affected by acetate or propionate, but was significantly reduced by butyrate. Trichostatin A, a specific inhibitor of histone deacetylase, also blocked the IFN-γ- and TNF-α-induced IP-10 mRNA expression, but the effects of trichostatin A were weaker than those of butyrate. The inhibitory effect of butyrate on IFN-γ-induced IP-10 release was not associated with STAT (signaling transducer and activator of transcription)-1α activation. We demonstrated that human colonic SEMFs are the local site for the secretion IP-10. The regulation of IP-10 release by IFN-γ and butyrate may play an important role in controlling chronic mucosal inflammation in pathological entities such as IBD.

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