Butyrate upregulates stromelysin-1 production by intestinal mesenchymal cells.
Nutritional factors and resident bacteria participate in the pathogenesis of 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 amplifying their response to signals in inflammatory conditions. Human mesenchymal cells were incubated with butyrate and then stimulated with cytokines. MMPs 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 interleukin-1beta-stimulated mesenchymal cells. Butyrate alone did not induce any change in MMP production or mRNA expression. It increased the acetylation of histones in mesenchymal cells. Furthermore, acetylation of histones (induced by trichostatin A) reproduced the effects of butyrate. Although butyrate 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.
Pender
S L
SL
Department of Paediatric Gastroenterology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London EC1A 7BE, United Kingdom. s.pender@soton.ac.uk
Quinn
J J
JJ
Sanderson
I R
IR
MacDonald
T T
TT
D000107:Acetylation; D002087:Butyrates / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005333:Fetus / Q000166:cytology / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007421:Intestine, Small / Q000166:cytology* / Q000201:enzymology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008648:Mesoderm / Q000166:cytology / Q000201:enzymology; D012333:RNA, Messenger / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002087:Butyrates; D004791:Enzyme Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D007375:Interleukin-1; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C012589:trichostatin A; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9