Atherogenic effects of TNF-α and IL-6 via up-regulation of scavenger receptors

• Published in: Cytokine (Philadelphia, Pa.) Vol. 58; no. 3; pp. 424 - 430
• Main Authors: Hashizume, Misato, Mihara, Masahiko
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2012
• Subjects: Arteriosclerosis; Atherogenesis; blood serum; Cardiovascular diseases; Cell Line; Flow Cytometry; Foam cell; foam cells; Humans; IL-6; Inflammation; Inflammatory diseases; Interleukin 6; Interleukin-6 - physiology; Lipoproteins (low density); LOX-1; LOX-1 protein; Macrophages; Macrophages - metabolism; metabolism; NF- Kappa B protein; patients; physiology; Real-Time Polymerase Chain Reaction; receptors; Receptors, Scavenger; Receptors, Scavenger - physiology; Rheumatoid arthritis; risk; Risk factors; scavenger receptors; Signal Transduction; SR-A; TNF-α; Tumor Necrosis Factor-alpha; Tumor Necrosis Factor-alpha - physiology; Up-Regulation; Up-Regulation - physiology; Foam cell; TNF-α; SR-A; LOX-1; IL-6
• ISSN: 1043-4666; 1096-0023; 1096-0023
• DOI: 10.1016/j.cyto.2012.02.010

► TNF-α and IL-6 each promoted foam cell formation, a pivotal process of oxLDL-mediated atherogenesis. ► αIL-6R Ab partially inhibited TNF-α-induced oxLDL accumulation. ► Serum from RA patients, but not serum of healthy subjects, induced foam cell formation. ► Foam cell formation induced by serum from RA serum was partially reverse by either αIL-6R Ab or TNF-α receptor (p75)-Fc. ► TNF-α, IL-6 and serum from RA patients each up-regulated the expression of SR-A, LOX-1 which uptake oxLDL. 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.