Augmented TLR2 expression on monocytes in both human Kawasaki disease and a mouse model of coronary arteritis.
BACKGROUND
Kawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis.


METHODS
Recruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009. Blood samples from KD patients were collected before and after IVIG treatment, and cardiovascular abnormalities were examined by transthoracic echocardiography. Wild-type male BALB/c mice (4-week-old) were intraperitoneally injected with LCWE (1 mg/mL) to induce coronary arteritis. The induced immune response in mice was examined on days 1, 3, 7, and 14 post injections, and histopathology studies were performed on days 7 and 14.


RESULTS
Both human KD patients and LCWE-treated mice developed coronary arteritis, myocarditis, valvulitis, and pericarditis, as well as elevated plasma levels of interleukin (IL)-2, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in acute phase. Most of these proinflammatory cytokines declined to normal levels in mice, whereas normal levels were achieved in patients only after IVIG treatment, with a few exceptions. Toll-like receptor (TLR)-2, but not TLR4 surface enhancement on circulating CD14+ monocytes, was augmented in KD patients before IVIG treatment and in LCWE-treated mice, which declined in patients after IVIG treatment.


CONCLUSIONS
This result suggests that that not only TLR2 augmentation on CD14+ monocytes might be an inflammatory marker for both human KD patients and LCWE-induced CAL mouse model but also this model is feasible for studying therapeutic strategies of coronary arteritis in human KD by modulating TLR2-mediated immune activation on CD14+ monocytes.
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and the Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung, Taiwan.
I-Chun
IC
Lin
Ho-Chang
HC
Kuo
Ying-Jui
YJ
Lin
Feng-Shen
FS
Wang
Lin
L
Wang
Shun-Chen
SC
Huang
Shao-Ju
SJ
Chien
Chien-Fu
CF
Huang
Chih-Lu
CL
Wang
Hong-Ren
HR
Yu
Rong-Fu
RF
Chen
Kuender D
KD
Yang
D000818:Animals; D002473:Cell Wall / Q000378:metabolism; D002675:Child, Preschool; D003324:Coronary Artery Disease / Q000139:chemically induced* / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007780:Lacticaseibacillus casei / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000378:metabolism*; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics* / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis* / Q000235:genetics*; D005719:gamma-Globulins / Q000008:administration & dosage
D018950:Lipopolysaccharide Receptors; C495342:TLR2 protein, human; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D005719:gamma-Globulins