Aloin Inhibits Interleukin (IL)-1beta-Stimulated IL-8 Production in KB Cells.

BACKGROUND: Interleukin (IL)-1beta, which is elevated in oral diseases including gingivitis, stimulates epithelial cells to produce IL-8 and perpetuate inflammatory responses. This study investigates stimulatory effects of salivary IL-1beta in IL-8 production and determines if aloin inhibits IL-1beta-stimulated IL-8 production in epithelial cells. METHODS: Saliva was collected from volunteers to determine IL-1beta and IL-8 levels. Samples from volunteers were divided into two groups: those with low and those with high IL-1beta levels. KB cells were stimulated with IL-1beta or saliva with or without IL-1 receptor agonist or specific mitogen-activated protein kinase (MAPK) inhibitors. IL-8 production was measured by enzyme-linked immunosorbent assay (ELISA). MAPK protein expression involved in IL-1beta-induced IL-8 secretion was detected by Western blot. KB cells were pretreated with aloin, and its effect on IL-1beta-induced IL-8 production was examined by ELISA and Western blot analysis. RESULTS: Saliva with high IL-1beta strongly stimulated IL-8 production in KB cells, and IL-1 receptor agonist significantly inhibited IL-8 production. Low IL-1beta-containing saliva did not increase IL-8 production. IL-1beta treatment of KB cells induced activation of MAPK signaling molecules as well as nuclear factor-kappa B. IL-1beta-induced IL-8 production was decreased by p38 and extracellular signal-regulated kinase (ERK) inhibitor treatment. Aloin pretreatment inhibited IL-1beta-induced IL-8 production in a dose-dependent manner and inhibited activation of the p38 and ERK signaling pathway. Finally, aloin pretreatment also inhibited saliva-induced IL-8 production. CONCLUSIONS: Results indicated that IL-1beta in saliva stimulates epithelial cells to produce IL-8 and that aloin effectively inhibits salivary IL-1beta-induced IL-8 production by mitigating the p38 and ERK pathway. Therefore, aloin may be a good candidate for modulating oral inflammatory diseases.