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Lithocholic Acid Alleviates Deoxynivalenol-Induced Inflammation and Oxidative Stress via PPARγ-Mediated Epigenetically Transcriptional Reprogramming in Porcine Intestinal Epithelial Cells
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-03-01 , DOI: 10.1021/acs.jafc.3c08044 Yanwei Li 1 , Chuyang Zhu 1 , Jiacheng Yao 1 , Cuipeng Zhu 1 , Zhaojian Li 1 , Hao-Yu Liu 1 , Miaonan Zhu 1 , Kaiqi Li 1 , Abdelkareem A Ahmed 2 , Shicheng Li 1, 3 , Ping Hu 1, 3 , Demin Cai 1, 3
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-03-01 , DOI: 10.1021/acs.jafc.3c08044 Yanwei Li 1 , Chuyang Zhu 1 , Jiacheng Yao 1 , Cuipeng Zhu 1 , Zhaojian Li 1 , Hao-Yu Liu 1 , Miaonan Zhu 1 , Kaiqi Li 1 , Abdelkareem A Ahmed 2 , Shicheng Li 1, 3 , Ping Hu 1, 3 , Demin Cai 1, 3
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Deoxynivalenol (DON) is a common mycotoxin that induces intestinal inflammation and oxidative damage in humans and animals. Given that lithocholic acid (LCA) has been suggested to inhibit intestinal inflammation, we aimed to investigate the protective effects of LCA on DON-exposed porcine intestinal epithelial IPI-2I cells and the underlying mechanisms. Indeed, LCA rescued DON-induced cell death in IPI-2I cells and reduced DON-stimulated inflammatory cytokine levels and oxidative stress. Importantly, the nuclear receptor PPARγ was identified as a key transcriptional factor involved in the DON-induced inflammation and oxidative stress processes in IPI-2I cells. The PPARγ function was found compromised, likely due to the hyperphosphorylation of the p38 and ERK signaling pathways. In contrast, the DON-induced inflammatory responses and oxidative stress were restrained by LCA via PPARγ-mediated reprogramming of the core inflammatory and antioxidant genes. Notably, the PPARγ-modulated transcriptional regulations could be attributed to the altered recruitments of coactivator SRC-1/3 and corepressor NCOR1/2, along with the modified histone marks H3K27ac and H3K18la. This study emphasizes the protective actions of LCA on DON-induced inflammatory damage and oxidative stress in intestinal epithelial cells via PPARγ-mediated epigenetically transcriptional reprogramming, including histone acetylation and lactylation.
中文翻译：
石胆酸通过 PPARγ 介导的猪肠上皮细胞表观遗传转录重编程减轻脱氧雪腐镰刀菌烯醇诱导的炎症和氧化应激
脱氧雪腐镰刀菌烯醇 (DON) 是一种常见的霉菌毒素，可引起人类和动物肠道炎症和氧化损伤。鉴于石胆酸（LCA）被认为可以抑制肠道炎症，我们旨在研究 LCA 对 DON 暴露的猪肠上皮 IPI-2I 细胞的保护作用及其潜在机制。事实上，LCA 挽救了 IPI-2I 细胞中 DON 诱导的细胞死亡，并降低了 DON 刺激的炎症细胞因子水平和氧化应激。重要的是，核受体 PPARγ 被确定为参与 IPI-2I 细胞中 DON 诱导的炎症和氧化应激过程的关键转录因子。研究发现 PPARγ 功能受到损害，可能是由于 p38 和 ERK 信号通路过度磷酸化所致。相比之下，LCA 通过 PPARγ 介导的核心炎症和抗氧化基因重编程来抑制 DON 诱导的炎症反应和氧化应激。值得注意的是，PPARγ 调节的转录调控可归因于共激活子 SRC-1/3 和辅阻遏物 NCOR1/2 募集的改变，以及修饰的组蛋白标记 H3K27ac 和 H3K18la。这项研究强调了 LCA 通过 PPARγ 介导的表观遗传转录重编程（包括组蛋白乙酰化和乳酰化）对 DON 诱导的肠上皮细胞炎症损伤和氧化应激的保护作用。
更新日期：2024-03-01
中文翻译：
石胆酸通过 PPARγ 介导的猪肠上皮细胞表观遗传转录重编程减轻脱氧雪腐镰刀菌烯醇诱导的炎症和氧化应激
脱氧雪腐镰刀菌烯醇 (DON) 是一种常见的霉菌毒素，可引起人类和动物肠道炎症和氧化损伤。鉴于石胆酸（LCA）被认为可以抑制肠道炎症，我们旨在研究 LCA 对 DON 暴露的猪肠上皮 IPI-2I 细胞的保护作用及其潜在机制。事实上，LCA 挽救了 IPI-2I 细胞中 DON 诱导的细胞死亡，并降低了 DON 刺激的炎症细胞因子水平和氧化应激。重要的是，核受体 PPARγ 被确定为参与 IPI-2I 细胞中 DON 诱导的炎症和氧化应激过程的关键转录因子。研究发现 PPARγ 功能受到损害，可能是由于 p38 和 ERK 信号通路过度磷酸化所致。相比之下，LCA 通过 PPARγ 介导的核心炎症和抗氧化基因重编程来抑制 DON 诱导的炎症反应和氧化应激。值得注意的是，PPARγ 调节的转录调控可归因于共激活子 SRC-1/3 和辅阻遏物 NCOR1/2 募集的改变，以及修饰的组蛋白标记 H3K27ac 和 H3K18la。这项研究强调了 LCA 通过 PPARγ 介导的表观遗传转录重编程（包括组蛋白乙酰化和乳酰化）对 DON 诱导的肠上皮细胞炎症损伤和氧化应激的保护作用。
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