Impact of curcumin on pro-inflammatory cytokine reduction in an inflammation-induced urothelium-on-a-chip model

This study presents a urothelium-on-a-chip platform, an innovative microfluidic system designed to replicate the physiological environment of the bladder. This platform effectively models the bladder mucosa by facilitating the co-culture of multiple cell types, including human urothelial (SV-HUC) and fibroblast (Hs27) cells. The system was employed to investigate urothelial injury, inflammation, and recovery, with a particular emphasis on the anti-inflammatory effects of curcumin in the context of lipopolysaccharide (LPS)-induced inflammation. The urothelium-on-a-chip system consists of three insert modules for culturing SV-HUC and Hs27 cells, interconnected via microfluidic channels. Single-cell (SV-HUC only) monocultures and multi-cell (SV-HUC and Hs27) co-cultures were established on the urothelium-on-a-chip platform. In both groups, inflammation was induced using LPS (1 µg/mL) for 24 h, followed by treatment with curcumin (10 µM) for an additional 24 h to evaluate its anti-inflammatory effects. Supernatants from the two groups were collected, and the levels of inflammatory cytokines IL-1β, IL-6, and TNF-α were quantified using ELISA. LPS treatment significantly increased IL-1β and IL-6 levels while slightly decreasing TNF-α. The co-culture systems exhibited notably higher levels of all three cytokines than the monoculture, indicating that fibroblast-urothelial interactions enhance the inflammatory response. Curcumin treatment following LPS exposure notably reduced cytokine levels under certain conditions. In the monoculture, curcumin completely suppressed IL-1β but did not induce a significant change in TNF-α and IL-6 levels. However, curcumin notably reduced all three cytokine levels in the co-culture system, highlighting its potential to modulate inflammation in a multi-cellular context. The ability to simulate inflammatory processes and assess treatments like curcumin provides a novel approach to researching bladder disease and screening potential therapies.