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

Abstract

The anti-inflammatory and antimicrobial properties of curcumin suggest its use as an anti-<i>Helicobacter pylori</i> (<i>H. pylori</i>) 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 <i>H. pylori</i>-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 <i>H. pylori</i>-infected human gastric mucosa. In an organ culture chamber, gastric biopsies from 35 patients were treated with and without 200 <i>μ</i>M curcumin. In <i>H. pylori</i>-infected patients (<i>n</i> = 21), IL-17 was significantly lower, both in gastric biopsies (<i>p</i> = 0.0003) and culture supernatant (<i>p</i> = 0.0001) while IDO significantly increased (<i>p</i> < 0.00001) in curcumin-treated sample compared with untreated samples. In a subgroup of <i>H. pylori</i>-infected patients (<i>n</i> = 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 (<i>p</i> < 0.00001). Curcumin downregulates IL-17 production through the induction of IDO in <i>H. pylori</i>-infected human gastric mucosa, suggesting its role in dampening <i>H. pylori</i>-induced immune-mediated inflammatory changes.