Fig. 7. I-287 inhibits PAR2-induced secretion of IL-8 cytokine in vitro and reduces CFA-induced inflammation in mice.

a, b Impact of I-287 (10 µM, 30 min) on hPAR2-promoted IL-8 cytokine release induced after 6 h stimulation with vehicle, hTrypsin (1 U/mL) or SLIGKV-NH₂ (100 µM) in culture medium of HCT 116 (a) and A549 (b) cells expressing hPAR2. Data are expressed as IL-8 concentration in pg/mL (mean ± SEM; n = 3–5; two-way ANOVA followed by Tukey’s post hoc test: ***p < 0.001 compared to control cells with vehicle; ^##p < 0.01 and ^###p < 0.001 compared to control cells with respective agonist). c Impact of I-287 on complete Freund’s adjuvant (CFA)-induced inflammation in mice. One hour after CFA injection, mice were given I-287 (50 mg/kg) or vehicle (95% TPGS – 5% NMP) by gavage. A group of animals received Ibuprofen (140 mg/kg) as a reference drug. The volume of the hindpaw was measured every hour to evaluate swelling/inflammation using a plethysmometer (mean ± SEM; n = 6 for vehicle and I-287 groups and n = 8 for Ibuprofen group; two-way repeated-measures ANOVA followed by Dunnett’s post hoc test: *p < 0.05 for I-287 vs. vehicle and ^##p < 0.01, ^###p < 0001 for Ibuprofen vs. vehicle).