Key resource table.

Over 2 million people in North America suffer from inflammatory bowel disease (IBD), a chronic and idiopathic inflammatory condition. While previous research has primarily focused on studying immune cells as a cause and therapeutic target for IBD, recent findings suggest that non-immune cells may also play a crucial role in mediating cytokine and chemokine signaling, and therefore IBD symptoms. In this study, we developed an organ-on-a-chip co-culture model of Caco2 epithelial and HUVEC endothelial cells and induced inflammation using pro-inflammatory cytokines TNF-α and IFN-γ. We tested different concentration ranges and delivery orientations (apical vs. basal) to develop a consistently inducible inflammatory response model. We then measured pro-inflammatory cytokines and chemokines IL-6, IL-8, and CXCL-10, as well as epithelial barrier integrity. Our results indicate that this model 1. induces IBD-like cytokine secretion in non-immune cells and 2. decreases barrier integrity, making it a feasible and reliable model to test the direct actions of potential anti-inflammatory therapeutics on epithelial and endothelial cells.

北美地区现有超过200万民众罹患炎症性肠病（inflammatory bowel disease, IBD）——这是一种慢性特发性炎症性疾病。既往研究多将免疫细胞作为IBD的致病机制与治疗靶点展开探究，而最新研究结果显示，非免疫细胞或许也在介导细胞因子与趋化因子信号通路、进而调控IBD症状的过程中发挥关键作用。本研究构建了Caco2上皮细胞与HUVEC内皮细胞的器官芯片共培养模型，采用促炎细胞因子TNF-α与IFN-γ诱导炎症反应；通过测试不同浓度范围与给药方向（顶侧vs基侧），优化得到可稳定诱导炎症反应的模型体系。随后，本研究检测了促炎细胞因子与趋化因子IL-6、IL-8、CXCL-10的表达水平，同时评估了上皮屏障完整性。研究结果表明，该模型可实现两点核心效果：1. 在非免疫细胞中诱导出IBD样的细胞因子分泌；2. 降低上皮屏障完整性。因此，该模型可作为可行且可靠的实验体系，用于检测潜在抗炎治疗药物对上皮与内皮细胞的直接作用。