RKIP induces apoptosis in mast cells sensitized by Echinococcus granulosus cyst fluid by inhibiting the PI3K/Akt/NF-κB signaling pathway
10.3969/j.issn.1002-2694.2025.00.077
- VernacularTitle:RKIP通过抑制PI3K/Akt/NF-κB信号通路诱导细粒棘球蚴囊液致敏的肥大细胞凋亡
- Author:
Xue-li PU
1
;
Yu-qian LI
;
Jing-ru ZHOU
;
Jia-ling WANG
;
Chun-sheng WANG
;
SUBI·TAILAITI
;
Jia-ying LIN
;
BATESURONG·BAYINA
;
Li-wei CAO
;
GULIGEIYA·PAREHATI
;
Jian-rong YE
Author Information
1. 新疆医科大学第一附属医院麻醉科,乌鲁木齐 830054
- Publication Type:Journal Article
- Keywords:
Echinococcus granulosus cyst fluid;
mast cell;
RKIP;
apoptosis
- From:
Chinese Journal of Zoonoses
2025;41(5):508-514
- CountryChina
- Language:Chinese
-
Abstract:
This study explored the effects and underlying mechanism of Raf kinase inhibitory protein(RKIP)on apoptosis in mast cells sensitized by Echinococcus granulosus cyst fluid.Bone marrow-derived mast cells(BMMCs)were isolated and cultured from RKIP knockout(KO)and wild-type(WT)C57BL/6 mice.Cells were divided into control and sensitized groups.The sensitized group was incubated for 24 h in RPMI1640 medium containing 10%serum from mice infected with E.granulosus,then activated for 3 h or 6 h with E.granulosus cyst fluid.The control group was incubated for 24 h in RPMI1640 medium,and then received an equal vol-ume of PBS.Cells and supernatants were collected for analysis.Flow cytometry was used to detect the expression of CD117 and FcεRⅠα on BMMCs.The levels of β-hexosaminidase,IL-4,and TNF-α in the supernatant were quantified with ELISA.Western blot analy-sis was used to assess expression changes in RKIP,apoptosis-related proteins,and pathway proteins in BMMC before and after sensi-tization.Flow cytometry analysis revealed that after 4 weeks of induction,the CD117 and FcεRⅠα double-positivity rates on both WT and KO BMMC exceeded 90%.ELISA indicated that the E.granulosus cyst fluid resulted in significantly greater β-hexosaminidase re-lease(F=16.88,P<0.05),and levels of IL-4(F=16.51,P<0.05)and TNF-α(F=9.78,P<0.05)in the KO sensitized group than the WT sensitized group.With respect to the WT control group,the WT sensitized group showed significantly down-regulated pro-tein expression levels of RKIP(F=8.20,P<0.05)and Bcl-2(F=101.40,P<0.01)after 3 h,but significantly up-regulated levels of p-PI3K(F=8.04,P<0.05),p-Akt(F=32.52,P<0.01),p-P65(F=13.29,P<0.05),and cleaved-caspase-3(F=46.34,P<0.01).With respect to the WT sensitized group,the KO sensitized group showed significantly up-regulated protein expression of p-PI3K(F=8.45,P<0.05),p-Akt(F=8.58,P<0.05),p-P65(F=11.02,P<0.05),and Bcl-2(F=84.50,P<0.001)after 3 h,but significantly down-regulated expression of cleaved-caspase-3(F=15.66,P<0.05).In conclusion,RKIP may inhibit the PI3K/Akt/NF-κB pathway,thereby inducing apoptosis in mast cells sensitized by E.granulosus cyst fluid.This process may help ease aller-gic reactions caused by mast cells in echinococcosis,thus offering a promising new approach for preventing and treating such reactions.
