Visfatin is a multifunctional protein involved in inflammatory immune stress. The aim of current study was to explore the role of visfatin in lipopolysaccharide (LPS)-induced intestinal mucosal inflammation and to confirm its cellular effect in inflammatory immune response through silencing of Toll-like receptors (TLRs). We divided Kunming mice into three groups: Saline group, LPS group, and LPS + visfatin group and performed hematoxylin and eosin staining, immunohistochemistry, quantitative polymerase chain reaction, Western blot, enzyme linked immunosorbent assay and RNA-seq analysis. Pretreatment of visfatin improves LPS-stimulated reduction of tight junction protein 1 (ZO-1) and secretory immunoglobulin A, inhibits overexpression of Claudin-1 and vascular endothelial growth factor, and reduces intestinal mucosal damage and inflammation. RNA-seq analysis of cellular transcriptomes indicated that visfatin is involved in down-regulation of mRNA level of TLR4 as well as attenuation of protein levels of TLR8 and nucleotide-binding oligomerization domain-containing protein 2, revealing that visfatin could reduce intestinal mucosal inflammation through TLR signaling pathway in mice ileum. In RAW264.7 cells, the genes silencing of Toll/IL-1R family, such as TLR4, TLR2, and IL-1R1, was accompanied by decreased expressions of inflammatory factors (TNF-α, IL-1β, IL-6 and MCP-1) along with lower cellular visfatin levels. Hence, visfatin maintains the intestinal mucosal barrier structure and attenuates the intestinal mucosal inflammation through the TLR signaling pathway. Likewise, the Toll/IL-1R family regulates the release of visfatin, which can participate in the inflammatory reaction through the regulation of inflammatory factors.

Visfatin 是一种参与炎症免疫应激的多功能蛋白质。本研究的目的是探讨内脂素在脂多糖 (LPS) 诱导的肠粘膜炎症中的作用，并通过沉默 Toll 样受体 (TLR) 来证实其在炎症免疫反应中的细胞作用。我们将昆明小鼠分为三组：盐水组、LPS 组和 LPS + visfatin 组，并进行苏木精和伊红染色、免疫组织化学、定量聚合酶链反应、蛋白质印迹、酶联免疫吸附试验和 RNA-seq 分析。visfatin 的预处理可改善 LPS 刺激的紧密连接蛋白 1 (ZO-1) 和分泌性免疫球蛋白 A 的减少，抑制 Claudin-1 和血管内皮生长因子的过度表达，并减少肠粘膜损伤和炎症。细胞转录组的 RNA-seq 分析表明，visfatin 参与了 TLR4 mRNA 水平的下调以及 TLR8 和含核苷酸结合寡聚化结构域蛋白 2 蛋白水平的减弱，揭示了 visfatin 可以通过以下方式减轻肠粘膜炎症小鼠回肠中的 TLR 信号通路。在 RAW264.7 细胞中，TLR4、TLR2 和 IL-1R1 等 Toll/IL-1R 家族基因的沉默伴随着炎症因子（TNF-α、IL-1β、IL-6 和 MCP）的表达降低。 -1) 以及较低的细胞内脂素水平。因此，visfatin通过TLR信号通路维持肠黏膜屏障结构并减轻肠黏膜炎症。同样，Toll/IL-1R 家族调节内脂素的释放，