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Mediators of Inflammation
Volume 2016, Article ID 1638916, 11 pages
http://dx.doi.org/10.1155/2016/1638916
Research Article

Negative Impact of Hypoxia on Tryptophan 2,3-Dioxygenase Function

1Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University, 40225 Düsseldorf, Germany
2Center for Advanced Research and Education, Asahikawa Medical University, Asahikawa 078-8510, Japan
3Neurogen Inc., 1-1-52-201 Nakahozumi, Ibaraki 567-0034, Japan
4Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Epidemiology, 17493 Greifswald-Insel Riems, Germany

Received 31 March 2016; Revised 14 June 2016; Accepted 26 June 2016

Academic Editor: José César Rosa Neto

Copyright © 2016 Frank Elbers et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Tryptophan is an essential amino acid for hosts and pathogens. The liver enzyme tryptophan 2,3-dioxygenase (TDO) provokes, by its ability to degrade tryptophan to N-formylkynurenine, the precursor of the immune-relevant kynurenines, direct and indirect antimicrobial and immunoregulatory states. Up to now these TDO-mediated broad-spectrum effector functions have never been observed under hypoxia in vitro, although physiologic oxygen concentrations in liver tissue are low, especially in case of infection. Here we analysed recombinant expressed human TDO and ex vivo murine TDO functions under different oxygen conditions and show that TDO-induced restrictions of clinically relevant pathogens (bacteria, parasites) and of T cell proliferation are abrogated under hypoxic conditions. We pinpointed the loss of TDO efficiency to the reduction of TDO activity, since cell survival and TDO protein levels were unaffected. In conclusion, the potent antimicrobial as well as immunoregulatory effects of TDO were substantially impaired under hypoxic conditions that pathophysiologically occur in vivo. This might be detrimental for the appropriate host immune response towards relevant pathogens.