ALK is required for NLRP3 inflammasome activation in macrophages
Journal Article
·
· Biochemical and Biophysical Research Communications
- Department of Critical Care Medicine, The Second People's Hospital of Changshu City, Changshu, Jiangsu, 215500 (China)
- Department of Pathology, The Second People's Hospital of Changshu City, Changshu, Jiangsu, 215500 (China)
Highlights: • ALK promotes LPS-induced NLRP3 priming. • ALK promotes ATP-induced NLRP3 activation. • ALK promotes NLRP3-NEK7 complex formation. • ALK-mediated lipid peroxidation promotes NLRP3 activation. The NLRP3 inflammasome is a key mediator of host immune responses through the induction of pyroptosis and the release of cytokines. Although the pathologic role of inflammasome in infection and sterile inflammation is well known, the mechanism and regulation of NLRP3 inflammasome activation remains obscure. Here, we report that anaplastic lymphoma kinase (ALK) is a novel regulator of NLRP3 inflammasome activation in macrophages. Pharmacologic or genetic inhibition of ALK through targeted drugs (ceritinib and lorlatinib) or RNAi blocked extracellular ATP-induced NLRP3 inflammasome activation in macrophages. Mechanically, ALK-mediated NF-κB activation was required for the priming step of NLRP3 upregulation, whereas ALK-mediated lipid peroxidation contributed to the sensing step of NLRP3-NEK7 complex formation. These studies indicate that inhibition of ALK could be utilized to treat NLRP3-related inflammatory diseases.
- OSTI ID:
- 23137055
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 501; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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