ReferenceID 6492
Wedelolactone facilitates Ser/Thr phosphorylation of NLRP3 dependent on PKA signalling to block inflammasome activation and pyroptosis
Cell Prolif
OBJECTIVES: Wedelolactone exhibits regulatory effects on some inflammatory diseases. However, the anti-inflammatory mechanism of wedelolactone has not been entirely unravelled. Therefore, the present study focuses on inv
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Record Fields
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- Reference Id
- 6492
- Evidence Id
- 23082
- Core Evidence Id
- 23082
- Source Reference Id
- 6286
- Herb2 Reference Id
- HBREF007083
- Subject Paper Key
- HBIN048224_32656909
- Pubmed Id
- 32656909
- Doi
- 10.1111/cpr.12868
- Paper Title
- Wedelolactone facilitates Ser/Thr phosphorylation of NLRP3 dependent on PKA signalling to block inflammasome activation and pyroptosis
- Paper Abstract
- OBJECTIVES: Wedelolactone exhibits regulatory effects on some inflammatory diseases. However, the anti-inflammatory mechanism of wedelolactone has not been entirely unravelled. Therefore, the present study focuses on investigating the mechanism of wedelolactone on NLRP3 inflammasome in macrophages and its influence on MSU-induced inflammation. MATERIALS AND METHODS: BMDM, J774A.1 and PMA-differentiated THP-1 macrophages were primed with LPS and then stimulated with ATP or nigericin or MSU crystal in the presence or absence of wedelolactone. The cell lysates and supernatants were collected to detect NLRP3 inflammasome components such as NLRP3, ASC and caspase 1, as well as pyroptosis and IL-1beta production. In addition, the anti-inflammatory effects of wedelolactone on MSU-induced peritonitis and arthritis mice were also evaluated. RESULTS: We found that wedelolactone broadly inhibited NLRP3 inflammasome activation and pyroptosis and IL-1beta secretion. Wedelolactone also block ASC oligomerization and speck formation. The inhibitory effects of wedelolactone were abrogated by PKA inhibitor H89, which also attenuated wedelolactone-enhanced Ser/Thr phosphorylation of NLRP3 at PKA-specific sites. Importantly, wedelolactone could abate MSU-induced IL-1beta production and neutrophils migration into peritoneal cavity, and reduced caspase 1 (p20) and IL-1beta expression in the joint tissue of MSU-induced arthritis. CONCLUSION: Our results indicate that wedelolactone promotes the Ser/Thr phosphorylation of NLRP3 to inhibit inflammasome activation and pyroptosis partly through potentiating PKA signalling, thus identifying its potential use for treating MSU-induced peritonitis and gouty arthritis.
- Journal
- Cell Prolif
- Publish Year
- 2020
- Experiment Subject
- mouse; pma-differentiated thp-1 macrophages
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Msu-induced Peritonitis; Inflammatory Diseases; Gouty Arthritis; Arthritis; Peritonitis
- Paper Title Cn
- Paper Title En
- Wedelolactone facilitates Ser/Thr phosphorylation of NLRP3 dependent on PKA signalling to block inflammasome activation and pyroptosis
- Bilingual Status
- semi_complete