6-formylindolo (3,2-b) carbazole (FICZ), a high-affinity aryl hydrocarbon receptor (AhR) ligand, plays a protective role in inflammatory bowel disease (IBD) through activation of AhR. Interleukin-6 (IL-6) induced intestinal epithelial barrier dysfunction is involved in the pathological process of IBD. In this study, we investigated the protective effects of FICZ on IL-6 induced intestinal epithelial barrier injury. Our data show that AhR activation by FICZ ameliorated colonic inflammation, decreased IL-6 and claudin-2 expression, and maintained intestinal barrier function in a mouse model of dextran sulphate sodium (DSS)-induced colitis. In Caco-2 and T84 intestinal epithelial cells, FICZ also prevented the increase of intestinal epithelial permeability and claudin-2 expression induced by IL-6. Depletion of AhR expression by small interfering (si)RNA reversed FICZ induced decrease of claudin-2. Furthermore, IL-6 induced upregulation of claudin-2 was required for increased caudal-related homeobox (CDX-2) and hepatocyte-nuclear factor (HNF)-1α. However, FICZ repressed the increase of CDX-2 and HNF-1α expression induced by IL-6. These results reveal the protective effects of FICZ on IL-6 induced disruption of intestinal epithelial barrier function through suppressing the expression of claudin-2. In addition, CDX-2 and HNF-1α are involved in the regulation of claudin-2 after IL-6 and FICZ treatment. Therefore, AhR-related compounds may be a potential pharmaceutical agent as a potential treatment of IBD.

高亲和力芳烃受体（AhR）配体6-甲酰基吲哚（3,2-b）咔唑（FICZ）通过激活AhR在炎症性肠病（IBD）中起保护作用。白介素6（IL-6）诱导的肠上皮屏障功能障碍参与了IBD的病理过程。在这项研究中，我们调查了FICZ对IL-6诱导的肠上皮屏障损伤的保护作用。我们的数据显示，FICZ的AhR激活可减轻结肠炎症，降低IL-6和claudin-2的表达，并在硫酸葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中维持肠屏障功能。在Caco-2和T84肠上皮细胞中，FICZ还阻止了IL-6诱导的肠上皮通透性和claudin-2表达的增加。小干扰（si）RNA逆转FICZ耗竭AhR表达会导致claudin-2减少。此外，IL-6诱导的claudin-2上调对于增加尾相关的同源盒（CDX-2）和肝细胞核因子（HNF）-1α是必需的。但是，FICZ抑制了IL-6诱导的CDX-2和HNF-1α表达的增加。这些结果揭示了FICZ通过抑制claudin-2的表达对IL-6诱导的肠上皮屏障功能破坏的保护作用。另外，在IL-6和FICZ处理后，CDX-2和HNF-1α参与claudin-2的调节。因此，与AhR相关的化合物可能作为IBD的潜在治疗剂。IL-6诱导的claudin-2上调是增加尾相关的同源盒（CDX-2）和肝细胞核因子（HNF）-1α所必需的。但是，FICZ抑制了IL-6诱导的CDX-2和HNF-1α表达的增加。这些结果揭示了FICZ通过抑制claudin-2的表达对IL-6诱导的肠上皮屏障功能破坏的保护作用。另外，在IL-6和FICZ处理后，CDX-2和HNF-1α参与claudin-2的调节。因此，与AhR相关的化合物可能作为IBD的潜在治疗剂。IL-6诱导的claudin-2上调是增加尾相关的同源盒（CDX-2）和肝细胞核因子（HNF）-1α所必需的。但是，FICZ抑制了IL-6诱导的CDX-2和HNF-1α表达的增加。这些结果揭示了FICZ通过抑制claudin-2的表达对IL-6诱导的肠上皮屏障功能破坏的保护作用。另外，在IL-6和FICZ处理后，CDX-2和HNF-1α参与claudin-2的调节。因此，与AhR相关的化合物可能作为IBD的潜在治疗剂。这些结果揭示了FICZ通过抑制claudin-2的表达对IL-6诱导的肠上皮屏障功能破坏的保护作用。另外，在IL-6和FICZ处理后，CDX-2和HNF-1α参与claudin-2的调节。因此，与AhR相关的化合物可能作为IBD的潜在治疗剂。这些结果揭示了FICZ通过抑制claudin-2的表达对IL-6诱导的肠上皮屏障功能破坏的保护作用。另外，在IL-6和FICZ处理后，CDX-2和HNF-1α参与claudin-2的调节。因此，与AhR相关的化合物可能作为IBD的潜在治疗剂。