Induction of MCP1, CCR2, and iNOS Expression in THP-1 Macrophages by Serum of Children Late After Kawasaki Disease

• Published in: Pediatric research Vol. 58; no. 6; pp. 1306 - 1310
• Main Authors: Cheung, Yiu-Fai, Karmin, O, Tam, Sidney C F, Siow, Yaw L
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.12.2005
• Subjects: Atherosclerosis - genetics; Biological and medical sciences; Cells, Cultured; Chemokine CCL2 - genetics; Child; Female; Gene Expression; General aspects; Humans; Lipids - blood; Macrophages - metabolism; Male; Medical sciences; Mucocutaneous Lymph Node Syndrome - complications; Mucocutaneous Lymph Node Syndrome - genetics; Mucocutaneous Lymph Node Syndrome - immunology; Nitric Oxide Synthase Type II - genetics; Receptors, CCR2; Receptors, Chemokine - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Serum - metabolism; Up-Regulation - genetics; Human; Kawasaki syndrome; Biological fluid; Pediatrics; Late; Enzyme; Induction; CCR2 chemokine receptor; Cardiovascular disease; Autoimmune disease; Chemokine receptor; CC chemokine; Gene expression; Nitric-oxide synthase; Vascular disease; Vasculitis; Systemic disease; Serum; Oxidoreductases; Triggering; Child; Monocyte chemoattractant protein 1; Macrophage
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1203/01.pdr.0000183360.79872.1c

Evidence of premature atherosclerosis late after Kawasaki disease (KD) is accumulating. Given the potential roles of monocyte chemoattractant protein-1 (MCP-1), chemokine receptor CCR-2, and inducible nitric oxide synthase (iNOS) in atherogenesis, we sought to determine whether serum obtained from children late after KD would induce expression of these genes in macrophages in vitro. A total of 79 subjects were studied, which comprised 57 KD patients, 33 of whom had coronary aneurysms, and 22 age-matched controls. Expression of MCP-1, CCR2, and iNOS mRNA in THP-1 macrophages in the presence of patient and control serum was quantified as a ratio to beta-actin mRNA and expressed as a percentage of control. MCP-1 expression was significantly increased in the presence of serum from patients with coronary aneurysms. Expression of CCR2 and iNOS was significantly increased when THP-1 macrophages were incubated with serum from patients with and without coronary aneurysms. The magnitude of induction of MCP-1, CCR2, and iNOS or in combinations correlated positively with serum high-sensitivity C-reactive protein (hs-CRP), and low-density lipoprotein (LDL) cholesterol levels and negatively with high-density lipoprotein (HDL) cholesterol level. In conclusion, the serum of patients with a history of KD induces expression of MCP-1, CCR2, and iNOS in THP-1 macrophages in vitro. Induction of these genes in vivo may be related to chronic inflammation and may have important implications for premature atherosclerosis.