Interleukin-enhanced binding factor 2 interacts with NLRP3 to inhibit the NLRP3 inflammasome activation
- State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072 (China)
- Institute of Medical Microbiology, Jinan University, Guangzhou 510632 (China)
Highlights: • The NLRP3 inflammasome activation is attenuated by PSMD10, BCL2L10, CTSS, and ILF2. • ILF2 represses inflammasome activation, pro-Casp-1 cleavege, and pro-IL-1β maturation. • ILF2 interacts with NLRP3 to inhibit the inflammasome activation in the cytoplasm. • ILF2 represses ATP-induced activation of endogenous NLRP3 inflammasome in macrophages. The activation of the NLRP3 inflammasome is a key process of host immune response that establishes the first line of defense against pathogen infections and cellular stresses, whereas excessive inflammasome activation may damage the hosts, and thus it must be precisely controlled. However, the mechanism underlying the repression of the NLRP3 inflammasome activation remains largely unknown. In this study, by establishing and using a reconstructed NLRP3 inflammasome activation system, we reveal that the NLRP3 inflammasome activation, pro-caspase-1 cleavage, and pro-interleukin-1β (pro-IL-1β) activation are repressed by the interleukin-enhanced binding factor 2 (ILF2). Further studies demonstrate that ILF2 represses the activation of NLRP3 inflammasome through interacting with the NACHT-associated domain (NAD) of NLRP3 and co-localized with NLRP3 in the cytoplasm of HEK293T cells. Finally, by generating a THP-1 cell line stably expressing ILF2 protein using the lentivirus infection system, we demonstrate that ILF2 represses ATP-induced activation of endogenous NLRP3 inflammasome in macrophages. Therefore, this study identifies a new role of ILF2 in the regulation of the NLRP3 inflammasome, and reveals a unique mechanism underlying the repression of the NLRP3 inflammasome activation.
- OSTI ID:
- 23125216
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 500; ISSN BBRCA9; ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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