Life Science Institute, Catholic University of Louvain (UCL), B-1348 Louvain-la-Neuve, Belgium.
Toxicol Lett. 2011 Oct 30;206(3):268-75. doi: 10.1016/j.toxlet.2011.08.010. Epub 2011 Aug 22.
This study aimed to investigate dose effects of dimethyl sulfoxide (DMSO) (0.05-1%) on the intestinal inflammatory response in confluent- and differentiated-Caco-2 cells stimulated with interleukin (IL)-1β or a pro-inflammatory cocktail for 24 h. Cyclooxygenase-2 (COX-2) activity was assayed by incubating inflamed cells with arachidonic acid and then measuring prostaglandin-E(2) (PGE(2)) produced. Soluble mediators (IL-8, IL-6, macrophage chemoattractant protein-1 (MCP-1), and COX-2-derived PGE(2)) were quantified by enzyme immunoassays and mRNA expression of 33 proteins by high throughput TaqMan Low Density Array. Data showed that DMSO decreased induced IL-6 and MCP-1 secretions in a dose-dependent manner (P<0.05), but not IL-8; these effects were cell development- and stimulus- independent. Moreover, in IL-1β-stimulated confluent-cells, DMSO dose-dependently reduced COX-2-derived PGE(2) (P<0.05). DMSO at 0.5% decreased significantly mRNA levels of 14 proteins involved in the inflammatory response (including IL-6, IL-1α, IL-1β, and COX-2). Thus, DMSO at low concentrations (0.1-0.5%) exhibits anti-inflammatory properties in the in vitro intestinal Caco-2 cell model. This point is important to be taken into account when assessing anti-inflammatory properties of bioactive compounds requiring DMSO as vehicle, such as phenolic compounds, in order to avoid miss-interpretation of the results.
本研究旨在探讨二甲基亚砜(DMSO)(0.05-1%)对经白细胞介素(IL)-1β或促炎混合物刺激 24 小时后汇合和分化的 Caco-2 细胞中肠道炎症反应的剂量效应。通过孵育发炎细胞与花生四烯酸,然后测量前列腺素-E2(PGE2)的产生来测定环氧化酶-2(COX-2)活性。通过酶免疫测定法和高通量 TaqMan 低密度阵列测定 33 种蛋白质的 mRNA 表达来定量可溶性介质(IL-8、IL-6、巨噬细胞趋化蛋白-1(MCP-1)和 COX-2 衍生的 PGE2)。结果表明,DMSO 以剂量依赖的方式降低诱导的 IL-6 和 MCP-1 分泌(P<0.05),但不降低 IL-8;这些作用与细胞发育和刺激无关。此外,在 IL-1β刺激的汇合细胞中,DMSO 以剂量依赖的方式降低 COX-2 衍生的 PGE2(P<0.05)。DMSO 浓度为 0.5%时,显著降低了 14 种参与炎症反应的蛋白质的 mRNA 水平(包括 IL-6、IL-1α、IL-1β和 COX-2)。因此,DMSO 在低浓度(0.1-0.5%)下在体外肠道 Caco-2 细胞模型中表现出抗炎特性。在评估需要 DMSO 作为载体的生物活性化合物(如酚类化合物)的抗炎特性时,这一点很重要,以避免对结果的错误解释。