Macrophage inflammatory protein-2: chromosomal regulation in rat small intestinal epithelial cells.
Nonpathogenic, resident bacteria participate in the pathogenesis of inflammation in the small intestine, but the molecular messages produced by such bacteria are unknown. Inflammatory responses involve the recruitment of specific leukocyte subsets. We, therefore, hypothesized that butyrate, a normal bacterial metabolite, may modulate chemokine secretion by epithelial cells, by amplifying their response to proinflammatory signals. We studied the expression of the chemokine, macrophage inflammatory protein-2 (MIP-2) by the rat small intestinal epithelial cell line, IEC-6. Cells were stimulated with lipopolysaccharide or with interleukin 1beta (IL-1beta) and incubated with sodium butyrate. Acetylation of histones was examined in Triton X acetic acid-urea gels by PAGE. Unstimulated IEC-6 cells did not secrete MIP-2. However, lipopolysaccharide and IL-1beta induced MIP-2 expression. Butyrate enhanced MIP-2 secretion both in lipopolysaccharide-stimulated and IL-1beta-stimulated enterocytes; but butyrate alone did not induce MIP-2 expression. Butyrate increased the acetylation of histones extracted from the nuclei of IEC-6 cells. Furthermore, acetylation of histones (induced by trichostatin A, a specific inhibitor of histone deacetylase) enhanced MIP-2 expression by cells stimulated with IL-1beta. In conclusion, trichostatin A reproduced the effects of butyrate on MIP-2 secretion. Butyrate, therefore, increases MIP-2 secretion in stimulated cells by increasing histone acetylation. We speculate that butyrate carries information from bacteria to epithelial cells. Epithelial cells transduce this signal through histone deacetylase, modulating the secretion of chemokines.
Ohno
Y
Y
Clinical Nutrition Research Center, Harvard Medical School and Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, MA 02129, USA.
Lee
J
J
Fusunyan
R D
RD
MacDermott
R P
RP
Sanderson
I R
IR
D000107:Acetylation; D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D054426:Chemokine CXCL2; D002630:Chemotactic Factors / Q000235:genetics*; D002875:Chromosomes; D046508:Culture Techniques; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D015846:Monokines / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D002087:Butyrates; D054426:Chemokine CXCL2; D002630:Chemotactic Factors; D006657:Histones; D006877:Hydroxamic Acids; D007375:Interleukin-1; D008070:Lipopolysaccharides; D015846:Monokines; D012333:RNA, Messenger; D020148:Butyric Acid; C012589:trichostatin A