Protective Effect of Kaempferol on LPS-induced Inflammation and Barrier Dysfunction in a Co-culture Model of Intestinal Epithelial cells and Intestinal Microvascular Endothelial Cells.

Yifei Bian, Yuanyang Dong, Jingjing Sun, Meng Sun, Qihang Hou, Yujiao Lai, Bingkun Zhang • 12/11/2019

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of intestinal mucosa and submucosa, characterized by the disruption of intestinal epithelial barrier, increased production of inflammatory mediators and excessive tissue injury. Intestinal epithelial cells, as well as microvascular endothelial cells, play important roles in IBD. To study the potential effects of kaempferol in IBD progress, we established a novel epithelial-endothelial cells co-culture model to investigate the intestinal inflammation and barrier function. Data demonstrated an obvious increased transepithelial electrical resistance (TEER) (1222 ± 60.40 Ωcm2 vs 1371 ± 38.77 Ωcm2), decreased flux of FITC(180.8 ± 20.06 μg/ml vs 136.7 ± 14.78 μg/ml) and up-regulated occludin and claudin-2 expression in Caco-2 that was specifically cocultured with endothelial cells. Meanwhile, 80 μM kaempferol alleviated the drop of TEER, the increase of FITC flux and the overexpression of Interleukin-8 (IL-8) induced by 1 μg/mL lipopolysaccharide (LPS). Additionally, kaempferol also ameliorated LPS-induced decrease of protein expression of zonula occludens-1 (ZO-1), occludin and claudin-2, together with the inhibited protein expressions of phosphorylation level of NF-κB and I-κB induced by LPS. Our results suggest that kaempferol alleviates the IL-8 secretion and barrier dysfunction of Caco-2 monolayer in LPS-induced epithelial-endothelial co-culture model via inhibiting NF-κB signaling pathway activation.

Citations: 83