Anti-inflammatory effect of indoleamine 2,3-dioxygenase 1 inhibition for lipopolysaccharide induced epididymitis

Abstract

ABSTRACT Introduction and Objective Even though antimicrobial therapy is received, some patients with epididymitis remaining inflammatory changes and led to refractory condition. Innovative therapy focused on the inflammatory changes is needed for epididymitis. Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first and rate-limiting step of tryptophan catabolism. IDO1 plays a key role in immune response and shows high expression in male genitalia. Furthermore, protective effect of IDO1 inhibition for various inflammatory disease was indicated in some reports. We hypothesize that IDO1 plays a central role for immunological reaction in epididymal inflammation. We investigated the relevance between IDO1 inhibition and epididymal inflammation. This study was approved by the safety committee for DNA experiments and the animal research committee of our facility (Approval No.14-35, 18-52). Materials and Methods Ten to twelve weeks old, C57BL/6 IDO1 knock out (IDO1 KO) mice were used through the research. Same conditional wild type (WT) mice were set as control. Lipopolysaccharide (LPS) 5μg/g(weight) was injected into epididymis from the vas deferens side. Epididymis was removed at a to 7 days after epididymitis modeling. Inflammatory changes in epididymis were investigated using histological, biochemical and immunohistochemical analysis. Series of these analysis were duplicated at least. Results Histological analysis using HE staining showed decreased effect of inflammation in IDO1 KO mice compared with WT mice. Proteomic analysis showed decreased effect of both inflammatory promoting cytokines (IL-1α, IL-6) and chemokines (CCL3, CXCL1) in IDO KO mice. On the other hand, increased effect of inflammatory inhibiting cytokines (IL-4, IL-10) were showed in IDO KO mice. Same results were obtained from immunohistochemical analysis using immunofluorescent staining. Conclusions IDO1 is involved in epididymal inflammation via cytokine and chemokine. IDO1 inhibition contribute to tissue protection for epididymitis. Therefore, IDO1 inhibition might be an innovative therapy for epididymitis. Disclosure Work supported by industry: no.