Objective-In this article, we studied the effect of acetyl-11-keto-␤-boswellic acid (AK␤BA), a natural inhibitor of the proinflammatory transcription factor NF-B on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE Ϫ/Ϫ ) mice. Methods and Results-Atherosclerotic lesions were induced by weekly LPS injection in apoE Ϫ/Ϫ mice. LPS alone increased atherosclerotic lesion size by Ϸ100%, and treatment with AK␤BA significantly reduced it by Ϸ50%. Moreover, the activity of NF-B was also reduced in the atherosclerotic plaques of LPS-injected apoE Ϫ/Ϫ mice treated with AK␤BA. As a consequence, AK␤BA treatment led to a significant downregulation of several NF-B-dependent genes such as MCP-1, MCP-3, IL-1␣, MIP-2, VEGF, and TF. By contrast, AK␤BA did not affect the plasma concentrations of triglycerides, total cholesterol, antioxidized LDL antibodies, and various subsets of lymphocytederived cytokines. Moreover, AK␤BA potently inhibited the IB kinase (IKK) activity immunoprecipitated from LPS-stimulated mouse macrophages and mononuclear cells leading to decreased phosphorylation of IB␣ and inhibition of p65/NF-B activation. Comparable AK␤BA-mediated inhibition was also observed in LPS-stimulated human macrophages. Conclusion-The

Lipid accumulation alters macrophage biology and contributes to lipid retention within the vessel wall. In this study, we investigated the role of adipophilin on triglyceride accumulation and lipid-droplet formation in THP-1-derived macrophages (THP-1 macrophages). In the presence of acetylated low-density lipoprotein, macrophages infected with an adenovirus expressing human adipophilin showed a 31% increase in triglyceride content and a greater number of lipid droplets compared with control cells. Incubation of macrophages with very low-density lipoprotein (VLDL) dramatically increased cellular triglyceride content similarly in control and adipophilin-overexpressing cells. By itself, VLDL increased adipophilin expression, which explains the lack of effect of adipophilin overexpression on cellular triglyceride content in macrophages loaded with VLDL. The lipid-droplet content of macrophages was increased by overexpression of adipophilin and ⁄ or loading with VLDL. In contrast, inhibition of adipophilin expression using siRNA prevented lipid-droplet formation and significantly reduced intracellular triglyceride content. Using inhibitors of b-oxidation and acyl-coenzyme A synthetase, results were obtained which suggest that adipophilin elevates cellular lipids by inhibition of b-oxidation and stimulation of long-chain fatty acid incorporation into triglycerides. Adipophilin expression in THP-1 macrophages altered the cellular content of different lipids and enhanced the size of lipid droplets, consistent with a role for adipophilin in human foam cell formation.