Short-Chain Fatty Acids Regulate Secretion of IL-8 from Human Intestinal Epithelial Cell Lines in vitro

Short-Chain Fatty Acids Regulate Secretion of IL-8 from Human Intestinal Epithelial Cell Lines in vitro
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DOI:
10.3109/08820139.2015.1085389
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发表时间:
2015-10-03
影响因子:
2.8
通讯作者:
Donkor, O.
Donkor, O.
中科院分区:
医学4区
文献类型:
--
作者:
Asarat, M.;Vasiljevic, T.;Donkor, O.

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短链脂肪酸(SCFA)包括醋酸、丙酸和丁酸,在上皮细胞和结肠细胞的免疫反应调节等生理功能中发挥着重要作用。人肠上皮细胞(IECs)通过不同的途径参与肠道免疫反应,如产生不同的免疫因子,包括白介素IL-8,作为中性粒细胞的趋化因子,从而增强炎症反应。因此,我们旨在评价单链脂肪酸对体外培养的IECs活力和IL-8产生的影响。将SCFA与正常肠上皮细胞系(T4056)或腺癌来源细胞系(HT-29)在大肠杆菌脂多糖(LPS)存在下共培养24-96h。测定细胞活力、细胞增殖、IL-8的产生及IL-8mRNA的表达。结果表明,20 mM的单链脂肪酸对T4056细胞无细胞毒作用,促进其生长,而对HT-29细胞的生长有抑制作用。SCFAs以不同的反应模式下调内毒素刺激的IL-8的分泌,但对非内毒素刺激的细胞释放IL-8无明显影响。综上所述,SCFAs对脂多糖刺激的IL-8的释放及IL-8mRNA的表达均有调节作用,这可能是SCFAs抗炎抗癌的机制之一。
Short-chain fatty acids (SCFAs) including acetate, propionate and butyrate play an important role in the physiological functions of epithelial cells and colonocytes, such as immune response regulation. Human intestinal epithelial cells (IECs) contribute in intestinal immune response via different ways, such as production of different immune factors including Interleukin (IL) IL-8, which act as chemoattractant for neutrophils, and subsequently enhance inflammation. Therefore, we aimed to evaluate the effects of SCFAs on IECs viability and production of IL-8 in vitro. SCFAs were co-cultured with either normal intestinal epithelial (T4056) or adenocarcinoma derived (HT-29) cell lines for 24-96h in the presence of E.coli lipopolysaccharides (LPS). Cell viability, proliferation, production of IL-8 and expression of IL-8 mRNA were determined in the cell cultures. The result showed that 20mM of SCFAs was non-cytotoxic to T4056 and enhanced their growth, whereas the growth of HT-29 was inhibited. The SCFAs down regulated LPS-stimulated IL-8 secretion with different response patterns, but no obvious effects on the release of IL-8 from non LPS- stimulated cells. In conclusion, SCFAs showed regulatory effect on release of LPS-stimulated IL-8 as well as the expression of mRNA of IL-8; these might explain the anti-inflammatory and anti-carcinogenic mechanism of SCFAs.