Oleuropein inhibited Th17 response and reduced intestinal IL-17 and IFN-γ release in dextran sulfate sodium (DSS)-induced acute colitis in C57BL/6 mice

Numerous studies on intestinal inflammation have established a critical role for the recently discovered Th17 cells, since an amount of this subtype of infiltrating leukocytes and their related cytokines are found in inflamed mucosa of colitic mice and in ulcerative colitis patients, as well. Once we demonstrated that oleuropein acts as an anti-inflammatory agent in such pathological condition, the present study attempts to determine if oleuropein exerts any effect on Th17 cells in a DSS-induced colitis model. Acute colitis was induced to C57BL/6 mice through oral administration of 3% DSS (w/v) in water for 7 days. Animals were randomly assigned to four groups: blank, control, oleuropein (100 mg/kg) and dexamethasone (2.5 mg/kg). After mice were sacrificed at day 8 by cervical dislocation, a piece of 0.5 cm of the distal part of the colon was cut and submitted to cytokine determination by ELISA. Mononuclear cells of lamina propria were isolated and stimulated with ionomycin (500 ng/mL) and phorbol myristate acetate (5 ng/mL). After 4h, cells were collected, incubated with antibodies against CD4, CD3, IL-17A, IFN-γ, and Rorγt, and analysed by FACS.

The percentage of CD4+ Rorγt+ cells and IL-17+IFN-γ+ expressing CD4+ Rorγt+ cells was higher in C group than in B group. Both subpopulations were inhibited in mice treated with oleuropein (25% and 48%, respectively) and with dexamethasone (40% and 30%, respectively). IL-17A and IFN-γ levels in colon samples were reduced by oleuropein (95% and 66% inhibition, respectively) and by dexamethasone (98% and 87% inhibition, respectively) respect to the control group.

In conclusion, oleuropein is able to reduce the Th17 response in DSS-induced acute colitis.