The human gastrointestinal (GI) tract is colonized by a highly diverse and complex microbial community (i.e., microbiota). The microbiota plays an important role in the development of the immune system, specifically mediating inflammatory responses, however the exact mechanisms are poorly understood. We have developed a mathematical model describing the effect of indole on host inflammatory signaling in HCT-8 human intestinal epithelial cells. In this model, indole modulates transcription factor nuclear factor κ B (NF-κB) and produces the chemokine interleukin-8 (IL-8) through the activation of the aryl hydrocarbon receptor (AhR). Phosphorylated NF-κB exhibits dose and time-dependent responses to indole concentrations and IL-8 production shows a significant down-regulation for 0.1 ng/mL TNF-α stimulation. The model shows agreeable simulation results with the experimental data for IL-8 secretion and normalized NF-κB values. Our results suggest that microbial metabolites such as indole can modulate inflammatory signaling in HTC-8 cells through receptor-mediated processes.

人类胃肠 (GI) 道被高度多样化和复杂的微生物群落（即微生物群）定殖。微生物群在免疫系统的发育中起着重要作用，特别是介导炎症反应，但其确切机制知之甚少。我们开发了一个数学模型来描述吲哚对 HCT-8 人肠上皮细胞中宿主炎症信号的影响。在该模型中，吲哚调节转录因子核因子 κ B (NF-κB) 并通过激活芳烃受体 (AhR) 产生趋化因子白细胞介素-8 (IL-8)。磷酸化的 NF-κB 对吲哚浓度表现出剂量和时间依赖性反应，IL-8 的产生显示出对 0.1 ng/mL TNF-α 刺激的显着下调。该模型通过 IL-8 分泌和标准化 NF-κB 值的实验数据显示了令人满意的模拟结果。我们的研究结果表明，吲哚等微生物代谢物可以通过受体介导的过程调节 HTC-8 细胞中的炎症信号。