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

J Periodontol. 2016 Jun;87(6):e108-15. doi: 10.1902/jop.2016.150447. Epub 2016 Mar 4.

Abstract

Background: Interleukin (IL)-1β, 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-1β in IL-8 production and determines if aloin inhibits IL-1β-stimulated IL-8 production in epithelial cells.

Methods: Saliva was collected from volunteers to determine IL-1β and IL-8 levels. Samples from volunteers were divided into two groups: those with low and those with high IL-1β levels. KB cells were stimulated with IL-1β 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-1β-induced IL-8 secretion was detected by Western blot. KB cells were pretreated with aloin, and its effect on IL-1β-induced IL-8 production was examined by ELISA and Western blot analysis.

Results: Saliva with high IL-1β strongly stimulated IL-8 production in KB cells, and IL-1 receptor agonist significantly inhibited IL-8 production. Low IL-1β-containing saliva did not increase IL-8 production. IL-1β treatment of KB cells induced activation of MAPK signaling molecules as well as nuclear factor-kappa B. IL-1β-induced IL-8 production was decreased by p38 and extracellular signal-regulated kinase (ERK) inhibitor treatment. Aloin pretreatment inhibited IL-1β-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-1β in saliva stimulates epithelial cells to produce IL-8 and that aloin effectively inhibits salivary IL-1β-induced IL-8 production by mitigating the p38 and ERK pathway. Therefore, aloin may be a good candidate for modulating oral inflammatory diseases.

Keywords: Aloe; KB cells; epithelial cells; interleukin-1beta; interleukin-8.

MeSH terms

  • Cells, Cultured
  • Emodin / analogs & derivatives*
  • Emodin / pharmacology
  • Humans
  • Interleukin-1beta / physiology*
  • Interleukin-6 / physiology
  • Interleukin-8 / metabolism*
  • KB Cells / metabolism
  • Mouth Diseases / metabolism*
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • p38 Mitogen-Activated Protein Kinases
  • Emodin
  • alloin