Modeling inter-kingdom regulation of inflammatory signaling in human intestinal epithelial cells. (2nd September 2020)

• Record Type: Journal Article
• Authors: Maiti, Shreya; Grivas, Genevieve; Choi, Kyungoh; Dai, Wei; Ding, Yufang; Acosta, Daniel Penarete; Hahn, Juergen; Jayaraman, Arul
• Is Part Of: Computers & chemical engineering. Volume 140(2020)
• Publication Date: 2020-09-02
• Subjects: Inflammatory signaling -- NF-κB -- AhR -- TNF-α -- Indole -- Mathematical model; Chemical engineering -- Data processing -- Periodicals; 660.0285
• DOI: 10.1016/j.compchemeng.2020.106954
• Languages: English
• ISSNs: 0098-1354

Abstract

Highlights: Indole modulates pro-inflammatory signaling. HTC-8 human colon-cancer cells were pre-treated with indole. Pre-treatment of indole reduced phosphorylation of NF-κB and IL-8 secretion. Computational model simulation results reflected experimental data. Abstract: 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.