Moderated Poster

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MP11-05: Therapeutic effect of indoleamine 2,3-dioxygenase inhibitor in epididymitis

Friday, May 12
1:00 PM - 3:00 PM
Location: BCEC: Room 151

Presentation Authors: Shin Ohira*, Ryoei Hara, Kurashiki City, Japan, Shigenobu Tone, Hatoyama-cho, Japan, Seitetsu Kin, Shinjiro Shimizu, Tomohiro Fujii, Yoshiyuki Miyaji, Atsushi Nagai, Kurashiki City, Japan

Introduction: Indoleamine 2, 3-dioxygenase (IDO) catalyzes the first and rate-limiting step of tryptophan catabolism and has been implicated in immune tolerance. IDO is known to be induced in various tissues during systematic bacterial infection and play a key role in immune response. In our previous research, we elucidated that epididymal IDO expression in the mouse is restricted to the caput region from segments 2 to 5 with peak of expression in segments 3 to 4. We hypothesize that IDO plays a central part of local immunological reaction in epididymis. We investigated all sorts of cytokines in epididymitis model of IDO knock out (IDO KO) mouse biochemically. Subsequently to the result of cytokines expression, we inhibited IDO in wild type (WT) mouse and clarified the function of IDO in epididymis.

Methods: Twelve weeks old C57BL/6J male mice (WT and IDO KO) were used in this study. Mice were injected with lipopolysaccharide (LPS) 4μg/g(weight) into epididymis on the side of the vas deferens. At 1,3,5 and 7 days after LPS injection, epididymides were removed. Histological changes were microscopically examined and evaluated. And then, cytokines were cyclopedically analyzed using cytokine assay (ELISA) for determining representative candidates. After that immunohistological changes were examined using immunostaing of representative cytokine candidates. In the following research, IDO inhibitor (1-Methyltryptophan: 1-MT 5mg/ml) was orally administrated to WT mice before LPS injection to their epididymides. At 1,3,5 and 7 days after the treatment, epididymides were removed. The role of IDO in epididymis was validated in terms of immunological reaction. Series of these experiments were duplicated at least.

Results: Prominent destruction of epididymal ductal structure and invasion of lymphocyte-predominant inflammatory cells were observed in epididymitis model of WT mice compared with that of IDO KO mice. Epididymal ductal structure in IDO KO mice was still maintained at day7 after LPS injection. Comprehensive cytokine assay (ELISA) showed that more than 2 folds of down-regulation of both inflammatory promoting cytokines (IL-1 alpha, IL-6) and chemokines (CCL3, CXCL1) were observed in epididymitis model of IDO KO mice compared with WT mice. On the other hand, more than 1.5 folds of up-regulation of inflammatory inhibiting cytokines (IL-4, IL-10) were observed in epididymitis model of IDO KO mice. The peak expression of IL-1 alpha, IL-6, CCL3 and CXCL1 were at day1 and that of IL-4 was at day3. The expression of IL-10 increased in time dependent manner. Same results were introduced from separate quantitative analysis and immunohistochemical staining. After treatment of IDO inhibition and LPS, IL-1 alpha, IL-6, CCL3 and CXCL1 were significantly down-regulated anytime in time series compared with WT mice using ELISA method (p<0.05). IL-4 and IL-10 were significantly up-regulated anytime in time series compared with WT mice (p<0.05). In the group of IDO inhibition, epididymal ductal structure was maintained at day7 after LPS injection and little invasion of inflammatory cells were observed anytime in time series.

Conclusions: IDO should be involved in epididymal immunological reaction via cytokines. To inhibit IDO would contribute to protection of epididymis tissue when inflammation occurs in epididymis. Therefore, IDO might be a novel target for the therapy of the epididymitis in addition to antibodiotics.

Source Of Funding: none

Shin Ohira, MD

Shin Ohira M.D.
Department of Urology, Kawasaki Medical School
577 Matsushima, Kurashiki City, Japan 701-0192

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MP07-13 Infertility: Basic Reserch & PathophysiologyⅠ

AUA2017 Presentation2
Title: Therapeutic effect of indoleamine 2,3-dioxygenase inhibitor in epididymitis
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MP11-05: Therapeutic effect of indoleamine 2,3-dioxygenase inhibitor in epididymitis



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