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- W1969620512 abstract "Costimulatory molecules play critical roles during cell-mediated immune responses. We undertook this study to determine whether CD154–CD40 interactions induced human endothelial cell (EC) activation via the nuclear factor (NF)-κB pathway, and whether the upregulation of monocyte-derived CD40 and CD80 is NF-κB pathway dependent. A CD154-expressing D1.1 cell–EC coculture with or without the NF-κB inhibitor BAY11-7082 was established to examine EC activation as indicated by CD62E expression. Peripheral blood mononuclear cell (PBMC)–EC cocultures were performed in the presence or absence of BAY11-7082; the expression of CD40 and CD80 on monocytes was analyzed by FACS. Allogeneic mixed lymphocyte–EC reaction (MLER) was performed to determine the inhibitory effects of BAY11-7082 to prevent lymphocyte proliferation. FACS demonstrated upregulation of EC-derived CD62E expression induced by CD154 expressing D1.1 cells. BAY11-7082 pretreated EC failed to upregulate CD62E after interaction with D1.1 cells. Monocytes upregulated CD40 and CD80 expression during PBMC–HEC interaction, and BAY11-7082 suppressed monocyte-derived CD40 and CD80 expression in a dose-dependent manner. The monocyte-derived CD86 expression was downregulated by NF-κB inhibitor. BAY11-7082 demonstrated inhibition of lymphocyte proliferation of allogeneic MLER. This study demonstrated that the NF-κB inhibitor BAY11-7082 prevented CD154–CD40 interaction-induced EC activation, suggesting that the activation of EC by T-cell–derived CD154 is via NF-κB pathway. The NF-κB inhibitor suppressed upregulation of monocytederived CD40 and CD80. Additionally, BAY11-7082 suppressed lymphocyte proliferation in response to allogeneic EC. These data indicated that NF-κB plays an important role in regulating costimulatory molecules in allogeneic immune responses, and strengthens the rationale for the use of NF-κB-directed therapy in allotransplantation." @default.
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- W1969620512 date "2008-10-01" @default.
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- W1969620512 title "A Nuclear Factor-κB Inhibitor BAY11-7082 Inhibits Interactions Between Human Endothelial Cells, T Cells, and Monocytes" @default.
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- W1969620512 doi "https://doi.org/10.1016/j.transproceed.2008.07.129" @default.
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