Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Immunol Cell Biol. 2011 Oct;89(7):817-22. doi: 10.1038/icb.2010.165. Epub 2011 Feb 15.
Increasing evidence suggests that the aryl hydrocarbon receptor (AhR) pathway has an important role in the regulation of inflammatory responses. Most recently, we have shown that the activation of the AhR pathway by a potent AhR agonist inhibits the development of dextran sodium sulfate (DSS)-induced colitis, a model of human ulcerative colitis, by the induction of prostaglandin E2 (PGE2) in the large intestine. Because several strains of probiotic lactic acid bacteria have been reported to inhibit DSS-induced colitis by unidentified mechanisms, we hypothesized that particular strains of lactic acid bacterium might have the potential to activate the AhR pathway, thereby inhibiting DSS-induced colitis. This study investigated whether there are specific lactic acid bacterial strains that can activate the AhR pathway, and if so, whether this AhR-activating potential is associated with suppression of DSS-induced colitis. By using AhR signaling reporter cells, we found that Lactobacillus bulgaricus OLL1181 had the potential to activate the AhR pathway. OLL1181 also induced the mRNA expression of cytochrome P450 family 1A1 (CYP1A1), a target gene of the AhR pathway, in human colon cells, which was inhibited by the addition of an AhR antagonist, α-naphthoflavon (αNF). In addition, mice treated orally with OLL1181 showed an increase in CYP1A1 mRNA expression in the large intestine and amelioration of DSS-induced colitis. Thus, OLL1181 can induce activation of the intestinal AhR pathway and inhibit DSS-induced colitis in mice. This strain of lactic acid bacterium has therefore the potential to activate the AhR pathway, which may be able to suppress colitis.
越来越多的证据表明,芳基烃受体(AhR)途径在调节炎症反应中起着重要作用。最近,我们已经表明,通过在大肠中诱导前列腺素 E2(PGE2),一种有效的 AhR 激动剂激活 AhR 途径可抑制葡聚糖硫酸钠(DSS)诱导的结肠炎的发展,这是人类溃疡性结肠炎的模型。因为已经报道了几种益生菌乳酸菌菌株通过未明机制抑制 DSS 诱导的结肠炎,所以我们假设特定的乳酸菌菌株可能具有激活 AhR 途径的潜力,从而抑制 DSS 诱导的结肠炎。本研究调查了是否存在可以激活 AhR 途径的特定乳酸菌菌株,如果存在,这种 AhR 激活潜力是否与抑制 DSS 诱导的结肠炎有关。通过使用 AhR 信号报告细胞,我们发现保加利亚乳杆菌 OLL1181 具有激活 AhR 途径的潜力。OLL1181 还诱导人结肠细胞中 AhR 途径的靶基因细胞色素 P450 家族 1A1(CYP1A1)的 mRNA 表达,AhR 拮抗剂α-萘黄酮(αNF)的加入抑制了这种表达。此外,用 OLL1181 口服治疗的小鼠在大肠中 CYP1A1 mRNA 表达增加,并改善 DSS 诱导的结肠炎。因此,OLL1181 可以诱导肠道 AhR 途径的激活并抑制小鼠的 DSS 诱导的结肠炎。这种乳酸菌菌株具有激活 AhR 途径的潜力,这可能能够抑制结肠炎。