Tedelind Sofia, Westberg Fredrik, Kjerrulf Martin, Vidal Alexander
Department of Molecular Pharmacology, AstraZeneca R&D Molndal, SE-431 83 Molndal, Sweden.
World J Gastroenterol. 2007 May 28;13(20):2826-32. doi: 10.3748/wjg.v13.i20.2826.
To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation.
The effect of SCFAs on cytokine release from human neutrophils was studied with ELISA. SCFA-dependent modulation of NF-kappaB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice.
Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFalpha release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-kappaB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures.
In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-kappaB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.
比较丁酸盐与另外两种短链脂肪酸（即乙酸盐和丙酸盐）的抗炎特性，后两者对炎症的影响文献记载较少。
采用酶联免疫吸附测定法（ELISA）研究短链脂肪酸对人中性粒细胞释放细胞因子的影响。在人结肠腺癌细胞系Colo320DM中评估短链脂肪酸对核因子κB（NF-κB）报告基因活性的调节作用。最后，在由结肠炎小鼠建立的小鼠结肠器官培养物中，分别采用逆转录聚合酶链反应（RT-PCR）和ELISA研究短链脂肪酸对基因表达和细胞因子释放的影响。
30 mmol/L的乙酸盐、丙酸盐和丁酸盐可降低脂多糖（LPS）刺激的中性粒细胞肿瘤坏死因子α（TNFα）释放，而不影响白细胞介素-8（IL-8）蛋白释放。所有短链脂肪酸均剂量依赖性抑制Colo320DM细胞中的NF-κB报告基因活性。丙酸盐剂量依赖性抑制结肠器官培养物中白细胞介素-6（IL-6）的信使核糖核酸（mRNA）和蛋白释放，比较研究显示，30 mmol/L的丙酸盐和丁酸盐可强烈抑制免疫相关基因表达，而乙酸盐效果较差。蛋白酶体抑制剂MG-132可产生类似的抑制作用，但p38丝裂原活化蛋白激酶（MAPK）抑制剂SB203580则不能。所有短链脂肪酸均可降低器官培养物中IL-6蛋白释放。
在本研究中，丙酸盐和丁酸盐在体外抑制NF-κB报告基因活性、免疫相关基因表达和细胞因子释放方面效果相当，而乙酸盐效果较差。我们的研究结果表明，除丁酸盐外，丙酸盐和乙酸盐可能对治疗包括炎症性肠病（IBD）在内的炎症性疾病有用。
