IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway

Abstract

Kawasaki disease (KD) is an acute vasculitis of pediatric populations that may develop coronary artery aneurysms if untreated. It has been regarded as the principal cause of acquired heart disease in children of the developed countries. Interleukin (IL)-37, as one of the IL-1 family members, is a natural suppressor of inflammation that is caused by activation of innate and adaptive immunity. However, detailed roles of IL-37 in KD are largely unclear. Sera from patients with KD displayed that IL-37 level was significantly decreased compared with healthy controls (HCs). QRT-PCR and western blot analyses showed that the expression level of IL-37 variant, IL-37b, was remarkably downregulated in human umbilical vein endothelial cells (HUVECs) exposed to KD sera-treated THP1 cells. Therefore, we researched the role of IL-37b in the context of KD and hypothesized that IL-37b may have a powerful protective effect in KD patients. We first observed and substantiated the protective role of IL-37b in a mouse model of KD induced by Candida albicans cell wall extracts (CAWS). In vitro experiments demonstrated that IL-37b alleviated endothelial cell apoptosis and inflammation via IL-1R8 receptor by inhibiting ERK and NFκB activation, which were also recapitulated in the KD mouse model. Together, our findings suggest that IL-37b play an effective protective role in coronary endothelial damage in KD, providing new evidence that IL-37b is a potential candidate drug to treat KD.

Melatonin alleviates vascular endothelial cell damage by regulating an autophagy‐apoptosis axis in Kawasaki disease

“…CAWS was prepared from C. albicans strain NBRC1358 (NITE Biological Resource Center, Japan), as previously described. 5 , 27 Briefly, C. albicans was cultured in C‐limiting medium at 400 rpm, 27°C, for 48 h. Following culture, an equal volume of ethanol was added, and the mixture was incubated overnight. The precipitate was then collected, dissolved in 250 ml of distilled water, and an equal volume of ethanol was added to it.…”

“…Beclin 1 is an essential protein that regulates autophagy by interacting with the anti‐apoptotic protein Bcl‐2. 25 , 26 Apoptosis caused by excessive immune activation and oxidative stress leads to vascular injury in KD patiens, 27 , 28 while autophagy has been shown to protect endothelial cells by attenuating inflammation in a KD mouse model. 21 Nevertheless, the role of the interaction between endothelial cell autophagy and apoptosis in the pathogenesis of KD remains uncertain.…”

CircRNA-3302 promotes endothelial-to-mesenchymal transition via sponging miR-135b-5p to enhance KIT expression in Kawasaki disease

“…* P < 0.05 and ** P < 0.01 were considered as statistically significant. The sample size was determined in accordance with previous literature [ 53 , 54 ], which performed similar experiments to obtain significant results. The variance was similar between the groups that were statistically compared.…”

Negative Regulation of the IL-1 System by IL-1R2 and IL-1R8: Relevance in Pathophysiology and Disease

“…In this context, IL-1R8 was required for the inhibitory role of IL-37 in the production of inflammatory mediators by monocytes ( 122 ). Finally, IL-37 alleviated endothelial cell apoptosis and inflammation via IL-1R8, by inhibiting ERK and NF-κB activation ( 123 ).…”