JNK inhibitor SP600125 inhibits interleukin-1β induced pyroptosis in βTC-6 cells
10.3760/cma.j.cn311282-20220907-00521
- VernacularTitle:JNK抑制剂SP600125抑制白细胞介素1β诱导的βTC-6细胞焦亡
- Author:
Wenmiao MA
1
;
Tengli LIU
;
Rui LIANG
;
Na LIU
;
Le WANG
;
Shusen WANG
;
Rongxiu ZHENG
Author Information
1. 天津医科大学总医院儿科，天津 300052
- Keywords:
Pyroptosis;
Diabetes mellitus;
GSDMD;
Interleukin-1β;
β cell line
- From:
Chinese Journal of Endocrinology and Metabolism
2023;39(5):430-434
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate whether interleukin(IL)-1β is involved in pyroptosis which leads to mouse islet β cell line βTC-6 cell damage, and to explore the role of JNK inhibitor SP600125 in inhibiting IL-1β induced βTC-6 cell pyroptosis.Methods:βTC-6 cell line and mouse islets were incubated with IL-1β for 48 h or intervened with both JNK inhibitor SP600125 and IL-1R antagonist IL-1Ra, then GSDMD expression and β cell pyroptosis morphology were detected by immunofluorescence staining of GSDMD and DAPI. The expression levels of Gsdmd, IL-1β and IL-18 mRNAs were detected by real time fluorescence PCR, and apoptosis was examined by Annexin-V/7-AAD staining combined with flow cytometry.Results:βTC-6 cell pyroptotic body was significantly increased in the IL-1β treated group compared with the control group, and the expressions of pyroptosis related genes Gsdmd, IL-1β, and IL-18 mRNA were significantly higher( P<0.05), and apoptosis was increased, suggesting that IL-1β effectively induced the βTC-6 cell pyroptosis, IL-1Ra prevented IL-1β induced βTC-6 cell pyroptosis. In the presence of JNK inhibitor SP600125, IL-1β treatment failed to induce the expressions of Gsdmd and IL-18 mRNA, markers of pyroptosis, and reduced the rate of apoptosis, indicating that SP600125 suppressed IL-1β induced βTC-6 cell pyroptosis. Conclusion:Pyroptosis is one of the mechanisms of βTC-6 cell impairment caused by IL-1β, and SP600125, a JNK inhibitor, can block the IL-1β induced pyroptosis pathway and has a potential role in inhibiting βTC-6 cell pyroptosis.
