Stemona alkaloids suppress the positive feedback loop between M2 polarization and fibroblast differentiation by inhibiting JAK2/STAT3 pathway in fibroblasts and CXCR4/PI3K/AKT1 pathway in macrophages

• Published in: International immunopharmacology 2019-07, Vol.72, p.385-394
• Main Authors: Ding, Qi, Sun, Jing, Xie, Weina, Zhang, Mian, Zhang, Chaofeng, Xu, Xianghong
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT1 protein; Alkaloids; Conditioning; CXCR4 protein; Differentiation; Feedback; Feedback loops; Fibroblast; Fibroblasts; Fibrosis; Interleukin 4; Janus kinase 2; Lipopolysaccharides; Lung diseases; Macrophage; Macrophages; Polarization; Positive feedback; Pulmonary fibrosis; SDF-1; SDF-1 protein; Stat3 protein; Stemona tuberosa; TGF-β1; Transcription; Transforming growth factor-b1
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.04.030

This study aimed to investigate the interaction between macrophages and fibroblasts in pulmonary fibrosis and the effects of total alkaloids of Stemona tuberosa (STA, 9 alkaloids with relative content of 91.2%) on them. The culture medium of LPS- or IL-4-induced macrophages was used as conditioned medium (CM) to co-culture with fibroblasts to study the effect of macrophages on the differentiation of fibroblasts. Similarly，the CM of TGF-β1-induced fibroblasts was co-culture with macrophages to study the effect of fibroblasts on the polarization of macrophages. The results showed that the TGF-β1 level in IL-4-induced (M2) rather than LPS-induced (M1) macrophages was significantly high (p