Liposomal Delivery of Purified Inhibitory-κBα Inhibits Tumor Necrosis Factor-α–Induced Human Vascular Smooth Muscle Proliferation

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Abstract
—Vessel injury results in the elaboration of various cytokines, including tumor necrosis factor-α (TNF-α), which may influence vascular smooth muscle cell (VSMC) function and contribute to atherogenesis. We tested the hypothesis that TNF-α–induced VSMC proliferation requires activation of the transcription factor nuclear factor-κB (NF-κB), which could be prevented by delivery of the NF-κB inhibitory peptide, IκBα. TNF-α induced concentration-dependent human VSMC proliferation, and neutralizing antibody to interleukin-6 reduced TNF-α–induced VSMC proliferation by 65%. In TNF-α–stimulated VSMCs, there was a 3-fold increase in NF-κB–dependent luciferase reporter activity that was associated with degradation of ΙκBα. To determine an essential role for NF-κB in TNF-α–induced VSMC proliferation, recombinant ΙκBα was introduced into VSMCs via liposomal delivery. Under these conditions, TNF-α–induced NF-κB nuclear translocation and DNA binding were inhibited, NF-κB–dependent luciferase activity was reduce...