25-hydroxyvitamin D3 exerts a protective effect on coronary artery lesions in a mouse model of Kawasaki disease by inhibiting JAK1/STAT3 and TLR4 pathways.

Abstract

Background: Kawasaki disease (KD) is an acute vasculitis in children, and the resultant inflammatory process can lead to coronary artery aneurysms. The study aimed to investigate the role of 25-hydroxyvitamin D₃ (25-OH-D₃), a stable circulating form of vitamin D₃, in KD mouse models.

Methods: The KD mouse model was established through intraperitoneal injection of 500 μg Lactobacillus casei cell wall extract (LCWE). 25-OH-D₃ was intraperitoneally injected to mice before and after LCWE injection. The mice were euthanized 7, 14, or 28 days after LCWE injection. Hematoxylin-eosin staining was performed to observe inflammation in mouse coronary artery tissues. ELISA was conducted to assess serum levels of inflammatory cytokines (tumour necrosis factor α and interleukin-1 beta ). Aorta areas and maximal aorta diameters were measured. Western blotting was performed to measure factors involved in JAK1/STAT3 and TLR4 signalling pathways.

Results: LCWE caused inflammatory cell infiltration in mouse coronary arteries, leading to high heart vessel inflammation scores, coronary artery lesion scores, and inflammatory cytokine levels within 28 days. In addition, LCWE induced the development of abdominal aorta aneurysms and dilatations. 25-OH-D₃ exerted a protective role in the KD mouse model by inhibiting coronary artery lesions and inflammation. Moreover, 25-OH-D₃ suppressed LCWE-induced activation of the JAK1/STAT3 and TLR4 pathways in coronary artery tissues.

Conclusion: 25-OH-D₃ ameliorates LCWE-induced coronary artery lesions and inflammation in mice by inhibiting the JAK1/STAT3 and TLR4 pathways.