中国人兽共患病学报2025，Vol.41Issue(5)：508-514,7.DOI:10.3969/j.issn.1002-2694.2025.00.077
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
RKIP induces apoptosis in mast cells sensitized by Echinococcus granulosus cyst fluid by inhibiting the PI3K/Akt/NF-κB signaling pathway
摘要
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.关键词
细粒棘球蚴囊液/肥大细胞/RKIP/细胞凋亡Key words
Echinococcus granulosus cyst fluid/mast cell/RKIP/apoptosis分类
基础医学引用本文复制引用
蒲雪莉,古丽给雅·帕热哈提,叶建荣,李玉倩,周静茹,王佳玲,王春生,苏比·泰来提,蔺佳英,巴特苏荣·巴一娜,曹力微..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[J].中国人兽共患病学报,2025,41(5):508-514,7.基金项目
国家自然科学基金项目(No.82060581) National Natural Science Foundation of China(No.82060581) （No.82060581）
