Neutrophil extracellular traps promote the activation of the NLRP3 inflammasome and PBMCs pyroptosis via the ROS-dependent signaling pathway in Kawasaki disease.

IF 4.8 2区 医学 Q2 IMMUNOLOGY
International immunopharmacology Pub Date : 2025-01-03 Epub Date: 2024-12-07 DOI:10.1016/j.intimp.2024.113783
Jing Jin, Yan Zhao, Yuying Fang, Yuting Pan, Panpan Wang, Zhidan Fan, Haiguo Yu
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引用次数: 0

Abstract

Kawasaki disease (KD) is an acute systemic vasculitis predominantly affecting infants and children under the age of 5. Recent studies have indicated that excessively released neutrophil extracellular traps (NETs) are involved in the progression of vasculitis. The purpose of this study was to investigate the role of NETs, especially their interaction with peripheral blood mononuclear cells (PBMCs), in the pathogenesis of KD. First, we demonstrated that the levels of NETs (cfDNA, MPO, and NE) in the serum of KD patients were significantly higher than those in healthy controls (HCs) and notably decreased after treatment. During the acute phase of KD, inflammatory markers (CRP and ESR) were positively correlated with NETs levels. Furthermore, we observed that neutrophils from KD patients in the acute phase produced elevated levels of NETs, and aspirin could effectively regulate the release of NETs. Additionally, NETs significantly increased the mRNA levels of NLRP3 and IL-1β in PBMCs, as well as the protein expression of NLRP3, caspase-1, ASC and gasdermin D, and the concentration of IL-1β in the cell supernatant. Moreover, NETs stimulated the production of reactive oxygen species (ROS) in PBMCs. N-acetylcysteine significantly reduced the expression of inflammatory factors and pyroptosis-related proteins in PBMCs. In conclusion, our findings suggest that NETs induce the generation of ROS, which in turn activates the NLRP3 inflammasome to mediate PBMCs pyroptosis and perpetuate inflammation in KD patients. This study reveals that targeting NETs or ROS could be a potential therapeutic approach for alleviating systemic inflammation, and that NETs may be a novel target for aspirin in the treatment of KD patients.

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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
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