Downregulation of Interleukin- (IL-) 17 through Enhanced Indoleamine 2,3-Dioxygenase (IDO) Induction by Curcumin: A Potential Mechanism of Tolerance towards Helicobacter pylori

Abstract

The anti-inflammatory and antimicrobial properties of curcumin suggest its use as an anti-Helicobacter pylori (H. pylori) agent, but mechanisms underlying its helpful activity are still not clear. Indoleamine 2,3-dioxygenase (IDO) promotes the effector T cell apoptosis by catalyzing the rate-limiting first step in tryptophan catabolism, and its high expression in H. pylori-infected human gastric mucosa attenuates Th1 and Th17 immune response. The aim of this study was to investigate the role of curcumin in modulating the expression of IL-17 and IDO in H. pylori-infected human gastric mucosa. In an organ culture chamber, gastric biopsies from 35 patients were treated with and without 200 μM curcumin. In H. pylori-infected patients (n=21), IL-17 was significantly lower, both in gastric biopsies (p=0.0003) and culture supernatant (p=0.0001) while IDO significantly increased (p<0.00001) in curcumin-treated sample compared with untreated samples. In a subgroup of H. pylori-infected patients (n=15), samples treated with curcumin in addition to IDO inhibitor 1-methyl-L-tryptophan (1-MT) showed a higher expression of IL-17 compared with untreated samples and curcumin-treated alone (p<0.00001). Curcumin downregulates IL-17 production through the induction of IDO in H. pylori-infected human gastric mucosa, suggesting its role in dampening H. pylori-induced immune-mediated inflammatory changes.