Abstract:
:The functional activities of the tumor suppressor promyelocytic leukemia protein (PML) are mostly associated with its nuclear location. In the present study, we discovered an unexpected role of PML in NLRP3 inflammasome activation. In PML-deficient macrophages, the production of IL-1β was strongly impaired. The expression of pro-IL-1β, NLRP3, ASC, and procaspase-1 was not affected in Pml(-/-) macrophages. PML deficiency selectively reduced the processing of procaspase-1. We further showed that PML is required for the assembly of the NLRP3 inflammasome in reconstitution experiment. All PML isoforms were capable of stimulating NLRP3 inflammasome activation. In Pml(-/-) macrophages, the generation of reactive oxygen species and release of mitochondrial DNA were decreased. The involvement of PML in inflammasome activation constitutes an important activity of PML and reveals a new mechanism underlying the inflammasome activation. In addition, downregulation of PML by arsenic trioxide suppressed monosodium urate (MSU)-induced IL-1β production, suggesting that targeting to PML could be used to treat NLRP3 inflammasome-associated diseases.
journal_name
Bloodjournal_title
Bloodauthors
Lo YH,Huang YW,Wu YH,Tsai CS,Lin YC,Mo ST,Kuo WC,Chuang YT,Jiang ST,Shih HM,Lai MZdoi
10.1182/blood-2012-05-432104subject
Has Abstractpub_date
2013-04-18 00:00:00pages
3185-94issue
16eissn
0006-4971issn
1528-0020pii
blood-2012-05-432104journal_volume
121pub_type
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