IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway
Open Access
- 3 June 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 12 (6), 1-14
- https://doi.org/10.1038/s41419-021-03852-z
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.Keywords
Funding Information
- National Natural Science Foundation of China (82000469, 81900240, 81970435, 81770502)
- Natural Science Foundation of Zhejiang Province (LY18H020012)
This publication has 43 references indexed in Scilit:
- Interleukin 37 (IL-37) Reduces High Glucose-Induced Inflammation, Oxidative Stress, and Apoptosis of Podocytes by Inhibiting the STAT3–Cyclophilin A (CypA) Signaling PathwayMedical Science Monitor, 2020
- Interleukin-37b inhibits the growth of murine endometriosis-like lesions by regulating proliferation, invasion, angiogenesis and inflammationMolecular Human Reproduction, 2020
- IL-37 isoform D downregulates pro-inflammatory cytokines expression in a Smad3-dependent mannerCell Death & Disease, 2018
- Interleukin‐18: Biological properties and role in disease pathogenesisImmunological Reviews, 2017
- Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart AssociationJournal of the American College of Cardiology, 2017
- miR-483 Targeting of CTGF Suppresses Endothelial-to-Mesenchymal TransitionCirculation Research, 2017
- GM-CSF primes cardiac inflammation in a mouse model of Kawasaki diseaseThe Journal of Experimental Medicine, 2016
- Salvianolic Acid B Down-regulates Matrix Metalloproteinase-9 Activity and Expression in Tumor Necrosis Factor-α-induced Human Coronary Artery Endothelial CellsChinese Medical Journal, 2015
- Endothelial Nlrp3 inflammasome activation associated with lysosomal destabilization during coronary arteritisBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2015
- The Potential Role of Cytokine‐Mediated Vascular Endothelial Activation in the Pathogenesis of Kawasaki DiseasePediatrics International, 1991