Induction of MCP1, CCR2, and iNOS expression in THP-1 macrophages by serum of children late after Kawasaki disease

Pediatr Res. 2005 Dec;58(6):1306-10. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis / genetics*
  • Cells, Cultured
  • Chemokine CCL2 / genetics*
  • Child
  • Female
  • Gene Expression
  • Humans
  • Lipids / blood
  • Macrophages / metabolism
  • Male
  • 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*
  • Serum / metabolism
  • Up-Regulation / genetics*


  • CCL2 protein, human
  • CCR2 protein, human
  • Chemokine CCL2
  • Lipids
  • Receptors, CCR2
  • Receptors, Chemokine
  • Nitric Oxide Synthase Type II