Triptolide ameliorates inflammation in AA rats by inhibiting pyroptosis through regulation of the lncRNA GAS5/miR-21/TLR4 signaling axis
10.13431/j.cnki.immunol.j.20240054
- VernacularTitle:雷公藤甲素通过lncRNA GAS5/miR-21/TLR4信号轴抑制细胞焦亡改善佐剂型关节炎大鼠炎症
- Author:
A'min WANG
1
;
Yunxiang CAO
;
Jian LIU
;
Nanfei ZHU
;
Hui WANG
Author Information
1. 230038 合肥,安徽中医药大学第一临床医学院
- Keywords:
Triptolide;
LncRNA GAS5/miR-21/TLR4;
Pyroptosis;
Immune inflammation;
Adjuvant arthritis
- From:
Immunological Journal
2024;40(5):418-424
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this study is to investigate the mechanism by which triptolide(TP)ameliorates inflammation in adjuvant arthritis(AA)rats by inhibiting pyroptosis through the lncRNA GAS5/miR-21/TLR4 signaling axis.Rats were divided into 4 groups:normal control group(NC),model control group(MC),triptolide group(TP)and methotrexate group(MTX),with 6 rats in each group.The AA rat model was established,and the general state,right foot-plantar swelling and arthritis index were observed;HE staining was used to detect the histopathological morphology of synovial joints of rats in each group;ELISA was used to detect the levels of inflammatory factors IL-1β,IL-6,IL-18 and TNF-α;fluorescence quantitative PCR was used to detect the mRNA expression levels of Caspase-1,IL-1β,NLRP3,GSDMD,GAS5,TLR4,NF-κB and miR-21;and Western blot was used to detect the expression levels of Caspase-1,NLRP3,GSDMD,NF-κB,Caspase-4 and TLR4 proteins.Compared with the NC group,rats in the MC group showed significantly higher levels of swelling,arthritis index(P<0.05)and inflammatory cell infiltration;compared with the MC group,the levels of IL-1β,IL-6,IL-18 and TNF-α were decreased in the TP and MTX groups(P<0.05),and the levels of Caspase-1,IL-1β,NLRP3,GSDMD,TLR4,NF-κB,miR-21 mRNA expression decreased,GAS5 mRNA expression increased(P<0.05),and the protein levels of Caspase-1,NLRP3,GSDMD,NF-κB,Caspase-4 and TLR4 decreased(P<0.05);compared with the MTX group,the TP group showed lower levels of IL-1β,IL-6,IL-18,TNF-α(P<0.05),and lower expression levels of Caspase-1,IL-1β,NLRP3,GSDMD,TLR4,NF-κB and miR-21 mRNA(P<0.05).In conclusion,triptolide may inhibit the production of pro-inflammatory factors and inhibit pyroptosis through the lncRNA GAS5/miR-21/TLR4 signaling axis,thus ameliorate inflammation in AA rats.
