Huang N, Katz J P, Martin D R, Wu G D
Department of Internal Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6144, USA.
Cytokine. 1997 Jan;9(1):27-36. doi: 10.1006/cyto.1996.0132.
Ulcerative colitis, an idiopathic inflammatory disease of the colonic mucosa, can be effectively treated by enemas containing short chain fatty acids (SCFA) such as butyrate, propionate, and acetate. The molecular mechanisms that lead to this response have not been well characterized. It is well known that intestinal inflammation leads to an alteration in patterns of epithelial differentiation with an increase in epithelial proliferation and an expansion of cell populations in an undifferentiated state. SCFAs such as butyrate are capable of inhibiting cell proliferation and inducing a differentiated phenotype in vitro. The Caco-2 colon cancer cell line was used to study the effect of SCFAs and the process of cellular differentiation on the expression of the pro-inflammatory cytokine, interleukin 8 (IL-8). SCFAs and trichostatin A, structurally unrelated compounds which both induce histone hyperacetylation, both led to a dose-dependent inhibition of IL-8 gene expression. Furthermore, spontaneous differentiation of Caco-2 cells by growth to a post-confluent state also inhibited the expression of IL-8. A possible mechanism by which SCFAs may be effective in the treatment of ulcerative colitis may be through their ability to increase histone acetylation states and inhibit the production of pro-inflammatory substances by the intestinal epithelium.
溃疡性结肠炎是一种结肠黏膜的特发性炎症性疾病，可通过含有短链脂肪酸（SCFA）如丁酸、丙酸和乙酸的灌肠剂有效治疗。导致这种反应的分子机制尚未得到充分表征。众所周知，肠道炎症会导致上皮分化模式改变，上皮增殖增加，未分化状态的细胞群体扩大。丁酸等短链脂肪酸能够在体外抑制细胞增殖并诱导分化表型。使用Caco-2结肠癌细胞系研究短链脂肪酸和细胞分化过程对促炎细胞因子白细胞介素8（IL-8）表达的影响。短链脂肪酸和曲古抑菌素A（结构上无关的化合物，均诱导组蛋白高乙酰化）均导致IL-8基因表达的剂量依赖性抑制。此外，Caco-2细胞生长至汇合后状态的自发分化也抑制了IL-8的表达。短链脂肪酸可能有效治疗溃疡性结肠炎的一种可能机制可能是它们能够增加组蛋白乙酰化状态并抑制肠道上皮细胞产生促炎物质。
