title: JNK is critical for the development of Candida albicans-induced vascular lesions in a mouse model of Kawasaki disease.
abstract: BACKGROUND
  Kawasaki disease (KD) is the most common systemic vasculitis of unknown etiology in children, and can cause the life-threatening complication of coronary artery aneurysm. Although a novel treatment strategy for patients with KD-caused vascular lesions is eagerly awaited, their molecular pathogenesis remains largely unknown. c-Jun N-terminal kinase (JNK) is a signaling molecule known to have roles in inflammation and tissue remodeling. The aim of this study was to elucidate significant involvement of JNK in the development of vascular lesions in a mouse model of KD.
  
  
  RESULTS
  We injected Candida albicans cell wall extract (CAWE) into 4-week-old C57BL/6 mice. Macroscopically, we found that CAWE caused the development of bulging lesions at coronary artery, carotid artery, celiac artery, iliac artery and abdominal aorta. Histological examination of coronary artery and abdominal aorta in CAWE-treated mice showed marked inflammatory cell infiltration, destruction of elastic lamellae, loss of medial smooth muscle cells and intimal thickening, which are similar to histological features of vascular lesions of patients with KD. To find the role of JNK in lesion formation, we evaluated the effects of JNK inhibitor, SP600125, on abdominal aortic lesions induced by CAWE. Interestingly, treatment with SP600125 significantly decreased the incidence of lesions and also protected against vascular inflammation and tissue destruction histologically, compared with the placebo treatment.
  
  
  CONCLUSIONS
  Our findings suggest that JNK is crucial for the development of CAWE-induced vascular lesions in mice, and potentially represents a novel therapeutic target for KD.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Fukuoka University, Fukuoka, 814-0180, Japan. Electronic address: yyoshika@fukuoka-u.ac.jp.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Yoshikane
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, 814-0180, Japan.
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Koga
authors.affiliation: Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, 514-8507, Japan; Mie University Research Center for Matrix Biology, Mie University, Tsu, 514-8507, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Imanaka-Yoshida
authors.affiliation: Section of Infection Biology, Department of Functional Bioscience, Fukuoka Dental College, Fukuoka, 814-0193, Japan.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Cho
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, 755-8505, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, 514-8507, Japan; Mie University Research Center for Matrix Biology, Mie University, Tsu, 514-8507, Japan.
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Fukuoka University, Fukuoka, 814-0180, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hashimoto
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Fukuoka University, Fukuoka, 814-0180, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirose
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, 755-8505, Japan; Graduate School of Health and Welfare, Yamaguchi Prefectural University, Yamaguchi, 753-8502, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002176:Candida albicans; D002177:Candidiasis / Q000150:complications; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009080:Mucocutaneous Lymph Node Syndrome / Q000201:enzymology* / Q000473:pathology*
chemical_list: D000873:Anthracenes; C432165:pyrazolanthrone; D048670:MAP Kinase Kinase 4
keywords: Candida albicans; JNK; Kawasaki disease; Vascular lesion