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VEGFによるHematopoietic Progenitor Cellの転写因子NF-κBに対する影響：小山倫浩^1,2、高橋孝宗³、Dmitry I Gabrilovich²、David P Carbone²、安元公正¹（¹産業医大・外、²Medical Center and ³Division of Nephrology, Vanderbilt University, USA）

VEGF inhibits TNFα-dependent activation of NF-κB and alters the subunit composition of NF-κB in hematopoietic progenitor cells: Tsunehiro OYAMA^1,2, Takamune TAKAHASHI³, Dmitry I GABRILOVICH², David P CARBONE², Kosei YASUMOTO¹ (¹Department of Surgery II, University of Occupational and Environmental Health, Kitakyushu; ¹Medical Center and ²Department of Medicine, Vanderbilt University, USA)

Professional antigen presenting cells such as dendritic cells (DC), are critical elements in the induction and maintenance of antitumor immune responses. Vascular endothelial growth factor (VEGF) is produced by tumors and promotes angiogenesis, but also inhibits dendritic cell differentiation. In this study, we investigated the effect of VEGF on activation of transcription factor NF-κB family members and IκB (a regulator of NF-κB) in human microvascular epithelial cells (HMEC), rat mesangial cells (RMC), and hematopoietic progenitor cells (HPC). TNFα induces NF-κB activation in human microvascular epithelial cells (HMEC), rat mesangial cells (RMC), and hematopoietic progenitor cells (HPC), and VEGF blocked this activation. Treatment with VEGF seemed to reduce TNFα-dependent degradation of IκBa in HMEC and HPC. In a supershift EMSA of HPC and confocal immunofluorescence examination of RMC, TNFα stimulated mostly RelA-containing complexes, whereas VEGF stimulation was associated with RelB-containing complexes. These data suggest that VEGF may act to inhibit DC differentiation by inhibiting IκBa degradation and altering the subunit composition of NF-κB.