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.

METHODS AND 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: Yukako Yoshikane, Mitsuhisa Koga, Kyoko Imanaka-Yoshida, Tamaki Cho, Yumi Yamamoto, Toshimichi Yoshida, Junichi Hashimoto, Shinichi Hirose, Koichi Yoshimura
• Journal: Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology (Cardiovasc Pathol) 2015 Jan-Feb Vol. 24 Issue 1 Pg. 33-40 ISSN: 1879-1336 [Electronic] United States
• PMID: 25242023 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anthracenes
• pyrazolanthrone
• MAP Kinase Kinase 4

Topics

• Animals
• Anthracenes (pharmacology)
• Candida albicans
• Candidiasis (complications)
• Disease Models, Animal
• Immunohistochemistry
• MAP Kinase Kinase 4 (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mucocutaneous Lymph Node Syndrome (enzymology, pathology)