Alimentary TractThe luminal short-chain fatty acid butyrate modulates NF-κB activity in a human colonic epithelial cell line☆,☆☆,★
Section snippets
Cell culture and treatments
HT-29 cells were purchased from American Type Culture Collection (Rockville, MD) and were propagated on tissue culture plastic with McCoy's 5A medium supplemented 10% fetal bovine serum, nonessential amino acids, streptomycin (50 μg/mL), and penicillin (50 U/mL).46 All medium components were purchased from Life Technologies (Gaithersburg, MD). TNF-α was purchased from R&D Systems and used at a final concentration 100 μg/mL. IL-1β was purchased from Promega (Madison, WI) and used at a
Influence of butyrate on NF-κB p50 dimer activity
Because evidence shows that butyrate may suppress mucosal inflammation,41, 42, 43 and many anti-inflammatory agents function by suppressing NF-κB activity (e.g., glucocorticoids and salicylates),44, 45 we determined the influence of butyrate on NF-κB in HT-29 cells. HT-29 cells possess a constitutive NF-κB DNA binding activity. Supershift analyses using antibodies to the NF-κB subunits indicate that this constitutive complex is a p50 dimer. As shown in Figure 1A, an antibody to the p50 subunit
Discussion
Butyrate plays a major role in many aspects of intestinal health and function. It is an important energy source for epithelial cells, plays a central role in regulating differentiation and apoptosis, and can suppress the development of colorectal cancer in laboratory animals.27, 35, 36, 37, 38, 39, 53, 56, 57 Evidence also indicates that butyrate may suppress intestinal inflammation.41, 42, 43 The mechanism of this potential anti-inflammatory effect is not clear. We have found that butyrate has
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Address requests for reprints to: Charles Giardina, Ph.D., Department of Molecular and Cell Biology, University of Connecticut, U-125, 75 North Eagleville Road, Storrs, Connecticut 06269-3125. e-mail: [email protected]; fax: (860) 486-4331.
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Supported by the National Institutes of Health (R29 CA 79656-01) and by a Research Starter Grant from the Pharmaceutical Research and Manufacturers of America Foundation (to C.G.).
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Drs. Inan and Rasoulpour contributed equally to this manuscript.