title: Induction of MCP1, CCR2, and iNOS expression in THP-1 macrophages by serum of children late after Kawasaki disease.
abstract: 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.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Grantham Hospital, The University of Hong Kong, China. xfcheung@hkucc.hku.hk
authors.forename: Yiu-Fai
authors.initials: YF
authors.lastname: Cheung
authors.forename: Karmin
authors.initials: K
authors.lastname: O
authors.forename: Sidney C F
authors.initials: SC
authors.lastname: Tam
authors.forename: Yaw L
authors.initials: YL
authors.lastname: Siow
mesh_terms: D050197:Atherosclerosis / Q000235:genetics*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics*; D002648:Child; D005260:Female; D015870:Gene Expression; D006801:Humans; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications* / Q000235:genetics / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics*; D044967:Serum / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics*
chemical_list: C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D008055:Lipids; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D052247:Nitric Oxide Synthase Type II