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Proliferation of peripheral blood mononuclear cells is suppressed by the indoleamine 2,3‐dioxygenase expression of interferon‐γ–treated skin cells in a co‐culture system
Author(s) -
Sarkhosh Kourosh,
Tredget Edward E.,
Li Yunyuan,
Kilani Ruhangiz T.,
Uludag Hasan,
Ghahary Aziz
Publication year - 2003
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1046/j.1524-475x.2003.11505.x
Subject(s) - indoleamine 2,3 dioxygenase , peripheral blood mononuclear cell , kynurenine , interferon gamma , immune system , interferon , immunology , cytokine , monocyte , human skin , cell culture , biology , tryptophan , in vitro , biochemistry , genetics , amino acid
Indoleamine 2,3‐dioxygenase (IDO) is an intracellular tryptophan‐oxidizing enzyme possessing various immunosuppressive characteristics. In this study, we report the possible use of this enzyme in an allogenic skin substitute to suppress the proliferation of immune cells. Human fetal skin fibroblasts and keratinocytes were treated with the cytokine interferon‐γ to induce expression of IDO mRNA and protein. IDO enzyme activity was evaluated by measurement of kynurenine levels in the interferon‐γ–treated and –untreated cells. Results of Northern analysis showed a dose‐dependent response in expression of IDO mRNA to the various concentrations of interferon‐γ used. Northern blot analysis also showed a time‐dependent expression of IDO in response to different durations of interferon‐γ treatment. The level of kynurenine measured, as the bioactivity of IDO enzyme, was significantly higher in the interferon‐γ–treated fibroblasts and keratinocytes compared to those of controls ( p < 0.001). To illustrate the immunosuppressive effects of IDO on immune cell proliferation, IDO‐expressing fibroblasts were cocultured with human peripheral blood mononuclear cells for a period of 5 days. Results of 3 H‐thymidine incorporation assays showed a significant reduction in proliferation of the mononuclear cells cocultured with IDO‐expressing skin cells compared to monocytes cocultured with control (non‐IDO‐expressing) skin cells ( p < 0.001). Furthermore, addition of the IDO‐inhibitor (1‐methyl‐D‐tryptophan) significantly reversed the immunosuppressive effects of IDO on monocyte proliferation ( p < 0.001). In conclusion, suppression of peripheral blood mononuclear cell proliferation due to interferon‐γ–induced IDO‐expression in allogenic human skin cells might shed new light on developing a nonrejectable allogenic skin substitute. (WOUND REP REG 2003;11:337–345)