VEGF expression in human macrophages is NF-kappaB-dependent: studies using adenoviruses expressing the endogenous NF-kappaB inhibitor IkappaBalpha and a kinase-defective form of the IkappaB kinase 2

摘要: Vascular endothelial growth factor (VEGF) is the most cell-specific angiogenic characterised to date, and it produced by a variety of cell types. In macrophages, VEGF has been shown be upregulated inflammatory mediator lipopolysaccharide (LPS) engagement CD40 ligand (CD40L). Because LPS CD40L activate nuclear factor-kappaB (NF-kappaB) in monocytes, we investigated this study whether production when stimulated with either or CD40L, NF-kappaB-dependent. We used adenoviral constructs over-expressing IkappaBalpha (AdvIkappaBalpha), endogenous inhibitor NF-kappaB, kinase-defective mutant IKK-2 (AdvIKK-2dn), an upstream activator IkappaBalpha, infect normal human monocyte-derived macrophages. observed that LPS-induced macrophages was almost completely inhibited (>90%) following transfer IkappaBalpha. addition, significant inhibition CD40L-induced infection AdvIkappaBalpha. Expression IKK-2dn decreased response approximately 50%, suggesting addition IKK-2, other kinases might involved NF-kappaB activation. These results show for first time dependent. regulates many genes immune responses, our adds cytokine list NF-kappaB-dependent cytokines.