Influences of scutellarin on ATP-induced inflammasome activation and pyroptosis in J774A.1 macrophages
10.3969/j.issn.1001-1978.2018.02.007
- VernacularTitle:灯盏花乙素对J774A.1巨噬细胞中ATP诱导的炎症小体活化和细胞焦亡的影响
- Author:
Yan-Yun JING
1
;
Chen-Guang LI
;
Liang YAN
;
Li-Hui XU
;
Wen-Jing BAI
;
Dong-Yun OUYANG
;
Xian-Hui HE
Author Information
1. 暨南大学生命科学技术学院免疫生物学系
- Keywords:
scutellarin;
pyroptosis;
macrophages;
NLRP3 inflammasome;
protein kinase A;
ATP
- From:
Chinese Pharmacological Bulletin
2018;34(2):174-180
- CountryChina
- Language:Chinese
-
Abstract:
Aim To explore the influences of scutellarin on ATP-induced NLRP3 inflammasome activation and pyroptosis,using LPS-primed murine macrophages J774A.1 as an inflammatory cell model,and to explore the underlying mechanism.Methods The effects of scutellarin on ATP-induced pyroptosis in murine J774A.1 macrophages were analyzed by propidium iodide (PI) staining assay.The levels of IL-1β,caspase-1 and HMGB1 in cell lysates and culture supernatants were analysed using Western blot.The levels of IL-1β in cell culture supernatants were measured by cytometric beads array (CBA).Results ATP significantly induced caspase-1 activation and mature IL-1β and HMGB1 release into the culture supernatants in LPS-primed murine J774A.1 macrophages,and induced pyroptosis.Scutellarin treatment dose-dependently inhibited ATP-induced caspase-1 activation,mature IL-1β and HMGB1 release,and pyroptosis.Notably,scutellarin's inhibitory effects on ATP-induced pyroptosis were markedly reversed by the adenylate cyclase inhibitor MDL12330A and selective protein kinase A (PKA) inhibitor H89.Conclusion Scutellarin inhibits NLRP3 inflammasome activation and pyroptosis by modulating the PKA activity in macrophages,thereby exhibiting anti-inflammatory activities.
