Modulation of complement component (C3 and factor B) biosynthesis by a histone deacetylase inhibitor in human intestinal epithelial cells.
Sodium butyrate enhances TNF-alpha-induced complement C3 secretion but suppresses TNF-alpha-induced factor B secretion in intestinal epithelial cells. To further evaluate the mechanism underlying these responses, we assessed the effects of trichostatin A, a compound structurally unrelated to butyrate and a potent inhibitor of histone deacetylase. The C3 and factor B secretion was evaluated by enzyme-linked immunosorbent assay (ELISA) and Northern blot, and the activation of transcription factor was assessed by an electrophoretic gel mobility shift assay (EMSA). Like sodium butyrate, trichostatin A enhanced TNF-alpha-induced C3 secretion, but suppressed TNF-alpha-induced factor B secretion. These effects were also observed at the level of mRNA. EMSAs indicated that trichostatin A weakly suppressed TNF-alpha-induced NF-kappaB and NF-IL6 activation. These observations differ from previous reports that sodium butyrate potently suppressed NF-kappaB activation but enhanced NF-IL6 activation. Trichostatin A modulated TNF-alpha-induced C3 and factor B secretion in a manner similar to that induced by sodium butyrate, suggesting that both sodium butyrate and trichostatin A exert certain counter-regulatory effects associated with histone hyperacetylation. However, it remains to be determined which factors other than histone acetylation are responsible for the counter-regulation of TNF-alpha-induced C3 and factor B gene expression.
Andoh
A
A
Department of Internal Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192, Japan.
Fujiyama
Y
Y
Shimada
M
M
Bamba
T
T
D015152:Blotting, Northern; D020148:Butyric Acid / Q000378:metabolism* / Q000494:pharmacology; D022762:CCAAT-Enhancer-Binding Proteins; D003176:Complement C3 / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D011415:Complement Factor B / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D003176:Complement C3; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D016328:NF-kappa B; D009687:Nuclear Proteins; D014409:Tumor Necrosis Factor-alpha; D020148:Butyric Acid; C012589:trichostatin A; D011415:Complement Factor B