title: Atherogenic effects of TNF-α and IL-6 via up-regulation of scavenger receptors.
abstract: Patients with chronic inflammatory disorders such as rheumatoid arthritis (RA) have a high risk of developing cardiovascular disease. We evaluated the effects of TNF-α and IL-6 on foam cell formation, a pivotal process in atherogenesis. Accumulation of intracellular oxidized LDL (oxLDL) was induced when THP-1/macrophages were stimulated with TNF-α or IL-6. TNF-α induced the expressions of scavenger receptors SR-A and LOX-1, and IL-6 induced SR-A expression. Inhibition of the NF-κB signaling markedly decreased TNF-α-induced foam cell formation and SR-A expression. Serum from RA patients, but not healthy subjects, induced foam cell formation, which was partially reversed by either IL-6 or TNF-α blockade in conjunction with inhibiting the induction of scavenger receptors. The present study clearly showed that in patients with chronic inflammation mediated by TNF-α and IL-6, these cytokines are directly implicated in atherosclerotic plaque formation.
authors.affiliation: Product Research Department, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Gotemba, Japan. hashizumemst@chugai-pharm.co.jp
authors.forename: Misato
authors.initials: M
authors.lastname: Hashizume
authors.forename: Masahiko
authors.initials: M
authors.lastname: Mihara
mesh_terms: D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051116:Receptors, Scavenger / Q000502:physiology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D015850:Interleukin-6; D051116:Receptors, Scavenger; D014409:Tumor Necrosis Factor-alpha