Hung Tran Van, Suzuki Takuya
Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University , Higashihiroshima 739-8528, Japan.
Ho Chi Minh City University of Food Industry , Ho Chi Min 15, Vietnam.
J Agric Food Chem. 2018 Jan 10;66(1):108-117. doi: 10.1021/acs.jafc.7b04233. Epub 2017 Dec 26.
Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, play an important role in the maintenance of intestinal homeostasis. In the present study, anti-inflammatory effects of SCFAs were examined in human intestinal Caco-2 cells and mouse colonic cultures. Stimulation of Caco-2 cells with tumor necrosis factor (TNF)-α induced interleukin (IL)-8 (TNF-α, 17.1 ± 7.2 vs Control, 1.00 ± 0.26, P < 0.01) and IL-6 expression (TNF-α, 21.7 ± 10.0 vs Control, 1.00 ± 0.28, P < 0.01) through the activation of nuclear factor κB p65, spleen tyrosine kinase, and mitogen-activated protein kinase pathways. Pretreatment of cells with acetate (5 mM, IL-8 1.23 ± 0.40, IL-6 2.19 ± 0.92, P < 0.01 ), propionate (2.5 mM, IL-8 2.45 ± 2.10, IL-6 2.19 ± 0.92, P < 0.01), or butyrate (0.625 mM, IL-8 1.44 ± 0.70, IL-6 2.31 ± 0.32, P < 0.01) suppressed inflammatory responses induced by TNF-α. Pharmacological inhibition of monocarboxylate transporter (MCT)-1 attenuated the suppression of inflammatory signals by SCFAs. High expression levels of CXC motif chemokine ligand 2 (CXCL2, an IL-8 homologue, DSS, 31.7 ± 9.8 vs Control, 1.00 ± 0.70, P < 0.01) and IL-6 (DSS, 17.5 ± 7.2 vs Control, 1.00 ± 0.68, P < 0.01) were observed in BALB/c mouse colonic cultures exposed to dextran sodium sulfate, whereas treatments with mixtures of SCFAs decreased these elevated expression levels (CXCL2 4.14 ± 2.88, IL-6 0.58 ± 0.28, P < 0.01). Our results suggest that SCFAs transported by MCT-1 suppress TNF-α-induced inflammatory signaling in intestinal cells.
短链脂肪酸（SCFAs），如乙酸盐、丙酸盐和丁酸盐，在维持肠道稳态中发挥着重要作用。在本研究中，我们检测了SCFAs在人肠道Caco-2细胞和小鼠结肠培养物中的抗炎作用。用肿瘤坏死因子（TNF）-α刺激Caco-2细胞可通过激活核因子κB p65、脾酪氨酸激酶和丝裂原活化蛋白激酶途径诱导白细胞介素（IL）-8（TNF-α刺激组为17.1±7.2，对照组为1.00±0.26，P<0.01）和IL-6表达（TNF-α刺激组为21.7±10.0，对照组为1.00±0.28，P<0.01）。用乙酸盐（5 mM，IL-8为1.23±0.40，IL-6为2.19±0.92，P<0.01）、丙酸盐（2.5 mM，IL-8为2.45±2.10，IL-6为2.19±0.92，P<0.01）或丁酸盐（0.625 mM，IL-8为1.44±0.70，IL-6为2.31±0.32，P<0.01）预处理细胞可抑制TNF-α诱导的炎症反应。单羧酸转运蛋白（MCT）-1的药理学抑制减弱了SCFAs对炎症信号的抑制作用。在暴露于葡聚糖硫酸钠的BALB/c小鼠结肠培养物中观察到CXC基序趋化因子配体2（CXCL2，一种IL-8同源物，葡聚糖硫酸钠组为31.7±9.8，对照组为1.00±0.70，P<0.01）和IL-6（葡聚糖硫酸钠组为17.5±7.2，对照组为1.00±0.68，P<0.01）的高表达水平，而用SCFAs混合物处理可降低这些升高的表达水平（CXCL2为4.14±2.88，IL-6为0.58±0.28，P<0.01）。我们的结果表明，由MCT-1转运的SCFAs可抑制肠道细胞中TNF-α诱导的炎症信号传导。
