JNK is critical for the development of Candida albicans-induced vascular lesions in a mouse model of Kawasaki Disease

Yoshikane, Yukako; Koga, Mitsuhisa; Imanaka‐Yoshida, Kyoko; Cho, Tamaki; Yamamoto, Yorihiro; Yoshida, Toshimichi; Hashimoto, Junichi; Hirose, Shinichi; Yoshimura, Kenichi

doi:10.1016/j.carpath.2014.08.005

Cited by 18 publications

(10 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of interest, a recent study using the Candida albicans extract-induced KD vasculitis mouse model also reported the development of systemic artery lesions in addition to coronary lesions 55 . Together, these observations suggest that in children with KD the incidence of AAA and dilation may be higher than currently appreciated, particularly in infants less than one year of age with very severe KD vasculitis and coronary aneurysms.…”

Section: Discussionmentioning

confidence: 99%

Role of Interleukin-1 Signaling in a Mouse Model of Kawasaki Disease–Associated Abdominal Aortic Aneurysm

Wakita

Kurashima

Crother

et al. 2016

ATVB

127

View full text Add to dashboard Cite

Objective Kawasaki disease (KD) is the most common cause of acquired cardiac disease in US children. In addition to coronary artery abnormalities and aneurysms, it can be associated with systemic arterial aneurysms. We evaluated the development of systemic arterial dilatation and aneurysms, including abdominal aortic aneurysm (AAA) in the Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis mouse model. Methods and Results We discovered that in addition to aortitis, coronary arteritis and myocarditis, the LCWE-induced KD mouse model is also associated with abdominal aorta dilatation and AAA, as well as renal and iliac artery aneurysms. AAA induced in KD mice was exclusively infrarenal, both fusiform and saccular, with intimal proliferation, myofibroblastic proliferation, break in the elastin layer, vascular smooth muscle cell loss, and inflammatory cell accumulation in the media and adventitia. Il1r−/−, Il1a−/−, and Il1a−/− mice were protected from KD associated AAA. Infiltrating CD11c+ macrophages produced active caspase-1 and caspase-1 or NLRP3 deficiency inhibited AAA formation. Treatment with IL-1R antagonist (Anakinra), anti-IL-1α, or anti-IL-1β mAb blocked LCWE-induced AAA formation. Conclusions Similar to clinical KD, the LCWE-induced KD vasculitis mouse model can also be accompanied by AAA formation. Both IL-1α and IL-1β play a key role, and that use of an IL-1R blocking agent that inhibits both pathways may be a promising therapeutic target not only for KD coronary arteritis, but also for the other systemic arterial aneurysms including AAA that maybe seen in severe cases of KD. The LCWE-induced vasculitis model may also represent an alternative model for AAA disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Role of Interleukin-1 Signaling in a Mouse Model of Kawasaki Disease–Associated Abdominal Aortic Aneurysm

Wakita

Kurashima

Crother

et al. 2016

ATVB

127

View full text Add to dashboard Cite

show abstract

“…The CAWS model shares some histological similarities with human Kawasaki disease pathology in that inflammation affects both the aortic root and the proximal region of the coronary arteries 190 . Inflammation can also affect non-coronary artery sites in 25% of CAWS-injected mice and can be observed in the lymph nodes, the kidneys and the liver 190,192 . CAWS-induced coronary artery lesions resemble those of human Kawasaki disease and are typically proliferative, granulomatous and characterized by intimal thickening with destruction of the elastic lamina and media 190 .…”

Section: Mouse Models Of Kawasaki Diseasementioning

confidence: 99%

Kawasaki disease: pathophysiology and insights from mouse models

2020

View full text Add to dashboard Cite

Kawasaki disease is a systemic vasculitis that affects infants and young children 1-3. Kawasaki disease is now the leading cause of acquired heart disease among children in North America, Europe and Japan 4,5. The cardiovascular sequelae resulting from childhood Kawasaki disease are increasingly recognized to extend into adulthood, and the disease is no longer considered self-limiting 6-9. The triggering agents for Kawasaki disease remain unidentified; however, results from our laboratory 10,11 and others 12,13 are consistent with the interpretation that a conventional antigen is probably responsible. Coronary arteritis and predominantly coronary artery aneurysms (CAAs) occur in up to 30% of untreated children, although this rate is reduced to 5-7% in children treated with high-dose intravenous immunoglobulin (IVIG) 3,14,15. IVIG treatment leads to CAA regression in 60-75% of patients with Kawasaki disease 16,17. However, the exact mechanisms by which IVIG reduces the rate of cardiovascular complications are unknown 18. Up to 15-20% of patients with Kawasaki disease do not respond to IVIG treatment, and these individuals have an increased rate of CAA development 3,15,19-21. Kawasaki disease is associated with infiltration of the coronary artery wall by a broad variety of innate and adaptive immune cells. Immunohistochemical analysis of human post-mortem tissues shows accumulation in the arterial wall of monocytes, macrophages and neutrophils 22,23 , and the presence of activated CD8 + T cells 24 as well Aetiological agents The causative agents initiating the disease have still not been identified >50 years after the first description of Kawasaki disease. However, the trigger is suspected to be of viral origin and to enter the body through the

show abstract

“…KD-like vasculitis can be induced in rabbit, swine, and mouse models by various methods (80)(81)(82)(83). The known genetic background and ease of genetic manipulation have made mouse models the preferred model to investigate molecular pathogenesis of KD and to discover its therapeutic targets (84)(85)(86)(87)(88).…”

Section: Insight From Experimental Studies With Animal Model For Kdmentioning

confidence: 99%

Aetiological Significance of Infectious Stimuli in Kawasaki Disease

2019

View full text Add to dashboard Cite

Kawasaki disease (KD) is a pediatric vasculitis syndrome that is often involves coronary artery lesions (e. g., coronary artery aneurysms). Although its causal factors and entire pathogenesis remain elusive, the available evidence indicates that the pathogenesis of KD is closely associated with dysregulation of immune responses to various viruses or microbes. In this short review, we address several essential aspects of the etiology of KD with respect to the immune response to infectious stimuli: 1) the role of viral infections, 2) the role of bacterial infections and the superantigen hypothesis, 3) involvement of innate immune response including pathogens/microbe-associated molecular patterns and complement pathways, and 4) the influence of genetic background on the response to infectious stimuli. Based on the clinical and experimental evidence, we discuss the possibility that a wide range of microbes and viruses could cause KD through common and distinct immune processes.

show abstract

JNK is critical for the development of Candida albicans-induced vascular lesions in a mouse model of Kawasaki Disease

Abstract: 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.

Cited by 18 publications

References 44 publications

Role of Interleukin-1 Signaling in a Mouse Model of Kawasaki Disease–Associated Abdominal Aortic Aneurysm

Role of Interleukin-1 Signaling in a Mouse Model of Kawasaki Disease–Associated Abdominal Aortic Aneurysm

Kawasaki disease: pathophysiology and insights from mouse models

Aetiological Significance of Infectious Stimuli in Kawasaki Disease

Contact Info

Product

Resources

About