Treatment with P28GST, a schistosome-derived enzyme, after acute colitis induction in mice: Decrease of intestinal inflammation associated with a down regulation of Th1/Th17 responses

Background P28GST, a 28Kd glutathione S-transferase enzymatic protein derived from a schistosome helminth prevents experimental colitiswhen administered subcutaneously in the presence of adjuvant by decreasing pro-inflammatory Th1/Th17 response. Given the antioxidant properties of P28GST, we evaluated its anti-inflammatory potential when administered locally after colitisinduction in the absence of adjuvant. Methods Colitiswas induced in BALB/c mice by rectal administrationof TNBS, followed by two intraperitoneal injections of P28GST at day 1 and day 2. Mice were sacrificed 48h after TNBS administration and evaluated for macroscopic and histological scores, myeloperoxidase (MPO) quantification and cytokine messenger RNA expression in the colonic tissues. Results Both clinical and histological scores significantly decreased in mice treated with P28GST at 5 or 50μg/kg when compared to vehicle- treated mice. A significant reduction of MPO was detected in colonic tissues from P28GST–treated mice, similarly to mice treated with methylprednisolone as the reference treatment. Pro-inflammatory cytokines TNF, IL-1β, and IL-6, mRNA as well as serum levels were down-regulated in mice colonic tissues treated with P28GST at 5 or 50μg/kg. In addition, a significant decrease of mRNA expression levels of T-bet, and ROR-γ, respective markers of Th1 and Th17 cells was observed. Whereas no significant effect was detected on Gata3mRNA, a marker of Th2 cells, the Arg/iNOS mRNA levels significantly increased in P28GST-treated mice, suggesting the induction of M2 macrophages. Conclusions These findings provide evidence that P28GST injected locally after colitisinduction induces a potent decrease of colitisinflammation in mice, associated to downregulation of Th1/Th17 response, and induction of anti-inflammatory alternatively activated macrophages.