Matrix metalloproteinase-9 in vascular lesions and endothelial regulation in Kawasaki disease.
BACKGROUND
Matrix metalloproteinases (MMPs) contribute to extracellular remodeling in Kawasaki disease (KD). MMP-9 is an essential vasculature-remodeling factor but its role in the vascular lesions of KD is not understood. This study focused on MMP-9 regulation via cytokines in endothelial cells (ECs).


RESULTS
Plasma and peripheral blood mononuclear cells were obtained from 30 KD patients, and 15 non-febrile and 25 febrile children. Plasma MMP-1, -2, -9, and tissue inhibitor of MMP (TIMP)-1 and -2 were measured by 2-step sandwich ELISA. Immunohistology was performed on coronary arterial lesions (CAL) from a patient who died of KD in the acute phase. MMP-9 mRNA expression in human umbilical ECs (HUVECs) treated with plasma or cytokines, and in mononuclear cells was measured by semi-quantitative reverse transcription-polymerase chain reaction. Plasma MMP-1, -2 and TIMP-2 levels were normal for KD. Plasma MMP-9 and TIMP-1 levels increased during the acute phase of the disease (P<0.001 vs each control). MMP-9 stained diffusely in CAL. MMP-9 mRNA levels were higher in HUVECs treated with plasma in the acute and convalescent phases. Interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha stimulated MMP-9 expression, whereas interferon (IFN)-gamma suppressed it. There was no MMP-9 mRNA elevation in mononuclear cells.


CONCLUSIONS
ECs are a source of MMP-9 in the vascular lesions of KD. MMP-9 is regulated by cytokines IL-1beta, IL-6, TNF-alpha and IFN-gamma.
Sakata
Koichi
K
Department of Pediatric Cardiology and Nephrology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
Hamaoka
Kenji
K
Ozawa
Seiichiro
S
Niboshi
Ayumi
A
Yahata
Tomoyo
T
Fujii
Maiko
M
Hamaoka
Akiko
A
Toiyama
Kentarou
K
Nishida
Masashi
M
Itoi
Toshiyuki
T
D001808:Blood Vessels / Q000201:enzymology / Q000473:pathology*; D002675:Child, Preschool; D003331:Coronary Vessels; D016207:Cytokines / Q000502:physiology; D042783:Endothelial Cells; D004730:Endothelium, Vascular / Q000201:enzymology*; D005260:Female; D005334:Fever; D006801:Humans; D007223:Infant; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis* / Q000235:genetics; D009080:Mucocutaneous Lymph Node Syndrome / Q000201:enzymology / Q000473:pathology*; D014471:Umbilical Veins / Q000166:cytology
D016207:Cytokines; D020780:Matrix Metalloproteinase 9