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). METHODS AND 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.
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). METHODS AND 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.
Authors: Andras Bratincsak; Blair N Limm-Chan; Vivek R Nerurkar; Lauren L Ching; Venu D Reddy; Eunjung Lim; Ralph V Shohet; Marian E Melish Journal: Contemp Clin Trials Date: 2017-12-05 Impact factor: 2.226
Authors: Karolina A Zielińska; Laura Van Moortel; Ghislain Opdenakker; Karolien De Bosscher; Philippe E Van den Steen Journal: Front Immunol Date: 2016-12-14 Impact factor: 7.561
Authors: Adriana H Tremoulet; Janusz Dutkowski; Yuichiro Sato; John T Kanegaye; Xuefeng B Ling; Jane C Burns Journal: Pediatr Res Date: 2015-08-03 Impact factor: 3.756