Butyrate upregulates stromelysin-1 production by intestinal mesenchymal cells

Nutritional factors and resident bacteria participate in the pathogenesis o f intestinal inflammation. However, the ways in which bacteria and complex diets might modulate matrix metalloproteinase (MMP) production are unknown. We hypothesized that butyrate might enhance production of MMPs, thus ampli fying their response to signals in inflammatory conditions. Human mesenchym al cells were incubated with butyrate and then stimulated with cytokines. M MPs and inhibitors were studied by Western blotting and quantitative RT-PCR . Acetylation of histones was examined in Triton X acetic acid-urea gels by PAGE. We showed that butyrate selectively enhanced the protein production and mRNA expression of stromelysin-1 in tumor necrosis factor-alpha- or int erleukin-1 beta -stimulated mesenchymal cells. Butyrate alone did not induc e any change in MMP production or mRNA expression. It increased the acetyla tion of histones in mesenchymal cells. Furthermore, acetylation of histones (induced by trichostatin A) reproduced the effects of butyrate. Although b utyrate is a major source of nutrient for the colonic epithelial cells, it modulates intestinal inflammation through the secretion of stromelysin-1 in stimulated stromal cells via the inhibition of histone deacetylase.