2006 Fiscal Year Final Research Report Summary
Therapeutic strategy for refractory Kawasaki disease in aspect of VEGF-VEGF receptor
| Project/Area Number |
17591071
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Tokyo Women's Medical University (2006)
Chiba University (2005) |
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Principal Investigator |
TERAI Masaru Tokyo Women's Medical University, Assistant Professor, 医学部, 助教授 (80207472)
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| Co-Investigator(Kenkyū-buntansha) |
YASUKAWA Kumi Chiba University, Instructor, 医学部附属病院, 助手 (10375769)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Kawasaki disease / p38 MAPK / 血管透過性 |
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| Research Abstract |
The p38 mitogen-activated protein kinase (MAPK) signaling pathway plays an important role in the pathogenesis of inflammatory diseases. p38 MAPK can be activated by proinflammatory cytokines and vascular endothelial growth factor. However, nothing is known about the role of p38 MAPK in acute Kawasaki disease (KD) where these inflammatory mediators are elevated. p38 MAPK was strongly activated in peripheral blood mononuclear cells from patients during acute KD inflammation and down-regulated in the convalescent phase of KD. Additionally, incubation of human umbilical vein endothelial cells (HUVEC) with KD sera before high-dose intravenous immune globulin (IVIG) induced a rapid increase in p38 MAPK phosphorylation. This activation of p38 MAPK was further enhanced when HUVEC were treated with post-IVIG sera from patients who failed to respond to initial IVIG and later developed coronary aneurysms (IVIG failure), but was down-regulated when treated with post-IVIG sera from patients who responded to initial IVIG and had normal coronaries (IVIG responder). Compared with sera from IVIG responders or febrile control, sera from IVIG failure induced not only the increase in HUVEC permeability but also the decrease in the tube forming activity of HUVEC. The p38 MAPK inhibitor blocked IVIG failure sera-induced vascular permeability. The same inhibitor restored the tube forming activity of HUVEC induced by sera from IVIG failure, a finding that was accompanied by enhancement of Erk1/2 MAPK activation. The findings suggest that in vitro endothelial cell dysfunction induced by serum from patients with refractory KD is modulated by p38 MAPK.
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