Bioluminescence imaging visualizes activation of nuclear factor-kappaB in mouse cardiac transplantation.

Background. The purpose of the current study was to evaluate the role of bioluminescence imaging (BLI) in the determination of nuclear factor (NF)-kappa B activation in cardiac allograft rejection and ischemia-reperfusion injury. Methods. To visualize NF-kappa B activation, luciferase transgenic mice under the control of a mouse NF-kappa B promoter (NF-kappa B-Luc) were used as donors or recipients of cardiac grafts. Alternatively, NF-kappa B-Luc spleen cells were adoptively transferred into Rag2(-/-) mice with or without cardiac allografts. BLI was performed posttransplantation to detect luciferase activity that represents NF-kappa B activation. Results. The results show that luciferase activity was significantly increased in the cardiac allografts when NF-kappa B-Luc mice were used as recipients as well as donors. Luciferase activity was also elevated in the wild-type cardiac allografts in Rag2(-/-) mice that were transferred with NF-kappa B-Luc spleen cells. CD 154 monoclonal antibody (mAb) therapy inhibited luciferase activity and induced long-term survival of cardiac allografts. toll-like receptor-9 ligand, CpG DNA, enhanced luciferase activity and abrogated tolerance induction by CD 154 mAb. Luciferase activity was also increased in ischemia-reperfusion injury of the cardiac grafts. Conclusion. BLI using Luc-NF-kappa B mice is a noninvasive approach to visualize the activation of NF-kappa B signaling in mouse cardiac allograft rejection and ischemia-reperfusion injury. CD154 mAb can inhibit NF-kappa B activation, which is reversed by toll-like receptor engagement.