Combined Effect of 25-Hydroxycholesterol and IL-1β on IL-8 Production in Human Colon Carcinoma Cell Line (Caco-2)

Interleukin-1 beta (IL-1β) is an important mediator in intestinal inflammation. IL-1β promotes IL-8 production, which can be modulated by a number of factors, including oxidative stress. Interestingly, oxysterols, which are thought to contribute to inflammation in atherosclerotic plaques, are also produced by intestinal epithelial cells. Thus, we investigated the effect of oxysterols, including 25-hydroxycholesterol and 7β-hydroxycholesterol, on IL-1β-induced IL-8 production in Caco-2 cells (a human colon carcinoma cell line). Pre-treatment of Caco-2 cells with 25-hydroxycholesterol significantly enhanced IL-1β-induced IL-8 expression at both mRNA and protein levels. However, 7β-hydroxycholesterol showed very little effect on IL-8 production. Furthermore, pre-treatment with 25-hydroxycholesterol, followed by IL-1β stimulation, enhanced IL-8 promoter activity beyond that observed with IL-1β alone. These results suggest that 25-hydroxycholesterol enhances IL-1β-induced IL-8 production, possibly by enhancing promoter activity.