Indole-3-carbinol is a potent inhibitor of ischemia-reperfusion-induced inflammation

Background: Ischemia-reperfusion (I/R) induces tissue inflammation, which is characterized by an increased leukocyte-endothelial cell interaction and leukocyte transmigration. These processes are mediated by the activation of the nuclear factor (NF) kappa B signaling pathway, resulting in an elevated expression of specific adhesion molecules. The phytochemical indole-3-carbinol (I3C) has been shown to exert anti-inflammatory effects by interfering with NF kappa B signal transduction. The aim of the present study was to investigate whether I3C is capable of counteracting the pathogenesis of I/R injury. Materials and methods: We investigated the inhibitory effect of I3C on endothelial surface protein expression during hypoxia and reoxygenation by flow cytometry. Moreover, the subcellular localization of NF kappa B was analyzed by immunofluorescence and Western blot. Adhesion protein levels on leukocytes after tumor necrosis factor-a stimulation were determined using flow cytometry. Finally, leukocyte-endothelial cell interaction and leukocyte transmigration during I/R was investigated in dorsal skinfold chambers of BALB/c mice by means of repetitive intravital fluorescence microscopy and immunohistochemistry. Results: I3C suppressed the expression of E-selectin and intercellular adhesion molecule-1 on human dermal microvascular endothelial cells by reducing the transcriptional activity of NF kappa B. Furthermore, surface protein levels of macrophage-1 antigen as well as activated lymphocyte function-associated antigen-1 were markedly reduced on I3C-treated leukocytes. In vivo, I3C treatment decreased the numbers of adherent and transmigrated leukocytes. This was associated with a reduced macromolecular leakage when compared with vehicle-treated controls. Conclusions: These novel results indicate that I3C reduces the expression of endothelial and leukocytic adhesion proteins, resulting in attenuated leukocyteeendothelial cell interactions during I/R. Accordingly, dietary supplements containing I3C may be beneficial for the treatment of I/R-induced inflammation. (C) 2017 Elsevier Inc. All rights reserved.