自噬
巨噬细胞极化
PI3K/AKT/mTOR通路
化学
肺纤维化
博莱霉素
下调和上调
M2巨噬细胞
纤维化
细胞生物学
癌症研究
信号转导
药理学
医学
生物
内科学
细胞凋亡
体外
巨噬细胞
生物化学
基因
化疗
作者
Peng Zhao,Zehui Cai,Yange Tian,Junzi Li,Kangchen Li,Minyan Li,Yunping Bai,Jiansheng Li
标识
DOI:10.1016/j.intimp.2021.108360
摘要
The M2 polarization of macrophages substantially contributes to the progression of pulmonary fibrosis (PF). Effective-compound combination (ECC), which is composed of isoliquiritigenin, icariin, nobiletin, peimine, and paeoniflorin, ameliorated bleomycin-induced PF in rats. Hence, we investigated the anti-PF mechanism of ECC with a focus on the suppression of M2 polarization in macrophages in vivo and in vitro.The PF rat model was generated via the intratracheal instillation of bleomycin. Histological changes, M2 macrophages, and profibrotic mediators were detected. The M2 polarization model was generated by incubating macrophages with IL-4. Quantitative PCR and Western blotting were used to measure mRNA and protein levels, respectively.ECC attenuated bleomycin-induced PF in rats, which might be associated with reduced macrophage infiltration, M2 polarization, and profibrotic mediator expression. Furthermore, ECC significantly suppressed M2 polarization in IL-4-treated macrophages, which was accompanied by the upregulation of autophagy. An autophagy inhibitor abrogated the inhibitory effect of ECC on M2 polarization. In addition, ECC decreased the levels of p-p70S6K/p-4EBP and p-AKT473/p-GSK3β, which are critical regulators of autophagy.ECC can ameliorate PF, which might be associated with the inhibition of M2 polarization through the promotion of autophagy via mTOR signaling suppression.
科研通智能强力驱动
Strongly Powered by AbleSci AI