Indoleamine 2,3-Dioxygenase Activation by Interferon Gamma in Vascular Endothelial Rat Cells Requires Noncanonical NF-κB Signaling

Indoleamine 2,3-dioxygenase (IDO) is an important enzyme in immune response regulation; cells that express IDO can suppress T-cell responses. Endothelial cells (ECs) play an important role in graft rejection. Therefore, we investigated the role of IDO expression by vascular ECs in immunoregulation. We demonstrated that interferon gamma can upregulate IDO expression in cultured ECs. Moreover, IDO induction by interferon gamma required IKK alpha activation, a part of the noncanonical NF-kappa B signaling pathway. In addition, I kappa B kinase alpha (IKK alpha) silencing resulted in significantly reduced IPO expression, demonstrating an essential role of NF-kappa B signaling pathway in IDO activation in vitro. These results may have an implication for regulating the immune response to alloantigens. The results obtained are important not only in understanding the role of ECs in the regulation of the transplantation immune response, but also in determining a potential therapeutic target for inhibiting allograft rejection.