Data_Sheet_5_Coral-Derived Endophytic Fungal Product, Butyrolactone-I, Alleviates Lps Induced Intestinal Epithelial Cell Inflammatory Response Through TLR4/NF-κB and MAPK Signaling Pathways: An in vitro and in vivo Studies.ZIP

Herein, we assessed the anti-inflammatory and intestinal barrier protective effects of butyrolactone-I (BTL-1), derived from the coral-derived endophytic fungus (Aspergillus terreus), using the LPS-induced IPEC-J2 inflammation model and the DSS-induced IBD model in mice. In IPEC-J2 cells, pretreatment with BTL-I significantly inhibited TLR4/NF-κB signaling pathway and JNK phosphorylation, resulting in the decrease of IL-1β and IL-6 expression. Interestingly, BTL-1 pretreatment activated the phosphorylation of ERK and P38, which significantly enhanced the expression of TNF-α. Meanwhile, BTL-1 pretreatment upregulated tight junction protein expression (ZO-1, occludin, and claudin-1) and maintained intestinal barrier and intestinal permeability integrity. In mice, BTL-1 significantly alleviated the intestinal inflammatory response induced by DSS, inhibited TLR4/NF-κB signaling pathway, and MAPK signaling pathway, thus reducing the production of IL-1, IL-6, and TNF-α. Further, the expression of tight junction proteins (ZO-1, occludin, and claudin-1) was upregulated in BTL-1 administrated mice. Therefore, it has been suggested that butyrolactone-I alleviates inflammatory responses in LPS-stimulated IPEC-J2 and DSS-induced murine colitis by TLR4/NF-κB and MAPK signal pathway. Thereby, BTL-1 might potentially be used as an ocean drug to prevent intestinal bowel disease.

本研究评估了源自珊瑚内生真菌（黑曲霉）的丁内酯-I（BTL-1）的抗炎和肠道屏障保护作用，通过LPS诱导的IPEC-J2炎症模型和DSS诱导的IBD小鼠模型进行。在IPEC-J2细胞中，预先用BTL-I处理显著抑制了TLR4/NF-κB信号通路和JNK磷酸化，导致IL-1β和IL-6表达降低。有趣的是，BTL-1预处理激活了ERK和P38的磷酸化，显著增强了TNF-α的表达。同时，BTL-1预处理上调了紧密连接蛋白的表达（ZO-1、occludin和claudin-1），并维持了肠道屏障和肠道渗透性的完整性。在老鼠身上，BTL-1显著缓解了由DSS诱导的肠道炎症反应，抑制了TLR4/NF-κB信号通路和MAPK信号通路，从而减少了IL-1、IL-6和TNF-α的产生。此外，BTL-1处理的老鼠中紧密连接蛋白（ZO-1、occludin和claudin-1）的表达也得到了上调。因此，有研究表明丁内酯-I通过TLR4/NF-κB和MAPK信号通路减轻了LPS刺激的IPEC-J2和DSS诱导的鼠结肠炎的炎症反应。因此，BTL-1有望作为一种海洋药物，用于预防肠炎。