Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation

Background: Butyrate, a fermentation product of intestinal bacteria, modifi es chromatin structure through histone acetylation, thereby altering gene t ranscription. IL-8 and MCP-1 are chemokines, expressed by intestinal epithe lial cells, which attract neutrophils and monocytes, respectively. We hypot hesized that butyrate may alter IL-8 and MCP-1 expression by intestinal epi thelial cells through histone acetylation. Materials and Methods: IL-8 and MCP-1 expression was measured by ELISA and RNA transfer blots. Acetylated histones were separated on acetic acid-urea- triton gels. Butyrate was compared to Trichostatin-A, a specific inhibitor of histone deacetylase and to other short chain fatty acids. Results: Caco-2 cells constitutively secreted MCP-1 but not IL-8. Butyrate reversibly decreased MCP-1 secretion. In contrast, butyrate increased IL-8 production. The effects of butyrate and Trichostatin-A were greater when ce lls were stimulated with IL-1 beta. Butyrate and Trichostatin-A both increa sed histone acetylation. Trichostatin-A and other shea chain fatty acids al tered chemokine secretion according to their effect on histone acetylation. Conclusions: Butyrate reversibly switches chemokine secretion by epithelial cells through histone acetylation. We speculate that butyrate carries info rmation from resident bacteria to epithelial cells. Epithelial cells transd uce this signal through histone acetylation modulating the secretion of che mokines.