Anti-inflammatory mechanism of indoleamine 2,3-dioxygenase 1 inhibition for autoimmune induced chronic prostatitis

Abstract

ABSTRACT Introduction and Objectives Evidence-based treatment for chronic prostatitis (CP) has not been established so far. Innovative therapy for CP is needed to establish evidence-based therapy. Indoleamine 2,3-dioxygenase1 (IDO1) catalyzes the first and rate-limiting step of tryptophan catabolism through the kynurenine pathway. IDO1 expression in prostate is higher than that of other organs. IDO1 is induced in various tissues during inflammatory disease. Furthermore, protective effect of IDO1 inhibition for inflammation was indicated in some reports. We hypothesize that IDO1 plays a central role for immunological reaction in CP. We investigated the relevance between IDO1 inhibition and CP using autoimmune induced CP model mice. This study was approved by the safety committee for DNA experiments and the animal research committee of our facility (Approval No.18-07 and 20-89). Materials and Methods Ten to twelve weeks old, IDO1 knock out (IDO1 KO) mice were used through the research. Same conditional wild type (WT) mice were set as control. Prostate gland extracted from Wister rat were used as prostate antigen (Pag) for mice. PAg 100µg / 100µl were injected into mice subcutaneously. After creating autoimmune induced CP model mice, inflammatory change in the prostate was investigated using histological, biochemical and immunohistochemical analysis. Results Histological analysis showed suppressive effect of inflammatory cells infiltration and interstitial fibrosis were observed in IDO1 KO CP model mice compared with that of WT CP model mice. Proteomic analysis showed decreased effect of lymphocyte and monocyte related cytokines (CCL2, CCL3) and fibrosis related cytokine (TIMP-1) in IDO1 KO CP model mice compared with that of WT CP model mice. Same results were obtained from immunohistochemical analysis using immunofluorescent stain. Conclusions IDO1 is involved in chronic inflammation via cytokines/chemokines in the prostate. IDO1 inhibition contribute to suppressive effect of chronic inflammation and fibrosis in the prostate. Therefore, IDO1 inhibition might be a novel target therapy for chronic prostatitis. Disclosure Work supported by industry: no.