Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon.
Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon.
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DOI：
10.1002/mnfr.202100539
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发表时间：
2021-10
影响因子：
5.2
通讯作者：
Safe S
中科院分区：
文献类型：
--
作者：
Chapkin RS;Davidson LA;Park H;Jin UH;Fan YY;Cheng Y;Hensel ME;Landrock KK;Allred C;Menon R;Klemashevich C;Jayaraman A;Safe S
本研究旨在探讨咖啡提取物在小鼠结肠细胞内对肠干细胞生长的作用机制和功能效应，以及对DSS所致小鼠肠屏障损伤的抑制作用。咖啡提取液诱导结肠来源的CACO2和YAMC细胞的AhR反应性细胞色素P1A1、细胞色素P1B1和UGT1A1基因的表达。组织特异性AhR基因敲除(AhRf/f x Lgr5-GFP-CreERT2 x Villin-Cre)和野生型(Lgr5-CreERT2 x Villin-Cre)小鼠是干细胞丰富有机物的来源，咖啡提取物和Norharman都是这些提取物中AhR活性成分抑制干细胞生长的来源。咖啡提取物还能抑制地塞米松对野生型(AhR+/+)小鼠肠道屏障功能的损伤和对IL-6、转化生长因子-β-1等炎症基因的影响，但不能抑制AhR-−/−小鼠的炎症反应。相比之下，咖啡在肠道特异的AhR基因敲除小鼠中没有显示出保护作用。咖啡提取物还促进了AhR活性微生物代谢物的全面形成。在结肠来源的细胞和小鼠的肠道中，咖啡诱导了几种AhR依赖的反应，包括基因表达，抑制肠道干细胞丰富的有机体的生长，以及抑制DSS诱导的肠道屏障破坏。我们得出结论，咖啡在肠道的抗炎作用部分是由于激活AhR信号。摘要示意图强调了咖啡提取物抑制DSS诱导的损伤、肠屏障功能和DSS诱导的粘膜炎症基因的AhR依赖的能力。咖啡提取物激活了结肠来源细胞系中的ah受体(AhR)反应基因。这些提取物和咖啡中一种AhR活性化合物Norharman也抑制了干细胞丰富的有机体的生长，并增强了DSS诱导的小鼠的肠道屏障功能。此外，咖啡提取物对干细胞和屏障功能的影响依赖于AhR。
This study investigates the mechanism of action and functional effects of coffee extracts in colonic cells, on intestinal stem cell growth and inhibition of DSS-induced intestinal barrier damage in mice. Aqueous coffee extracts induced Ah receptor (AhR) -responsive CYP1A1, CYP1B1 and UGT1A1 gene expression in colon-derived Caco2 and YAMC cells. Tissue-specific AhR knockout (AhRf/f x Lgr5-GFP-CreERT2 x Villin-Cre), wild-type (Lgr5-CreERT2 x Villin-Cre) mice were sources of stem cell enriched organoids and both coffee extracts and norharman, an AhR-active component of these extracts inhibited stem cell growth. Coffee extracts also inhibited DSS-induced damage to intestinal barrier function and DSS-induced mucosal inflammatory genes such as IL-6 and TGF-β1 in wild-type (AhR+/+) but not AhR−/− mice. In contrast, coffee did not exhibit protective effects in intestinal-specific AhR knockout mice. Coffee extracts also enhanced overall formation of AhR-active microbial metabolites. In colon-derived cells and in the mouse intestine, coffee induced several AhR-dependent responses including gene expression, inhibition of intestinal stem cell-enriched organoid growth and inhibition of DSS-induced intestinal barrier damage. We conclude that the anti-inflammatory effects of coffee in the intestine are due, in part, to activation of AhR signaling. Summary diagram highlighting the AhR-dependent ability of coffee extract to suppress DSS-induced damage, intestinal barrier function and DSS-induced mucosal inflammatory genes. Coffee extracts activated Ah receptor (AhR) responsive genes in colon-derived cell lines. These same extracts and norharman, an AhR-active compound in coffee also inhibited growth in stem cell enriched organoids and enhanced intestinal barrier function in DSS-induced mice. Moreover, the effects of coffee extracts on stem cells and barrier function were AhR-dependent.
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DOI：
10.1056/nejmoa1112010
发表时间：
2012-05-17
期刊：
The New England journal of medicine
影响因子：
--
作者：
Freedman ND;Park Y;Abnet CC;Hollenbeck AR;Sinha R
通讯作者：
Sinha R
影响因子：
9.8
作者：
Gungorduk, Kemal;Ozdemir, Aykut;Sanci, Muzaffer
通讯作者：
Sanci, Muzaffer
影响因子：
37.8
作者：
Ding M;Bhupathiraju SN;Satija A;van Dam RM;Hu FB
通讯作者：
Hu FB
影响因子：
3.2
作者：
DeLuca, Jennifer A. A.;Allred, Kimberly F.;Allred, Clinton D.
通讯作者：
Allred, Clinton D.
影响因子：
11.4
作者：
Han, Huajun;Davidson, Laurie A.;Chapkin, Robert S.
通讯作者：
Chapkin, Robert S.