%0 Journal Article
%T D-4F, an apolipoprotein A-I mimetic, suppresses IL-4 induced macrophage alternative activation and pro-fibrotic TGF-¦Â1 expression
%A Chaoxiong Zhang
%A Jia You
%A Jingyuan Xiong
%A Linshen Xie
%A Xuejiao Song
%A Ying Shi
%A Zhengshu Wang
%J Pharmaceutical Biology
%D 2019
%R https://doi.org/10.1080/13880209.2019.1640747
%X Abstract Context: We reported that D-4F, an apolipoprotein A-I (Apo A-I) mimetic polypeptide with 18 d-amino acids, suppressed IL-4 induced macrophage alternative activation and TGF-¦Â1 expression in phorbol 12-myristate 13-acetate (PMA) treated human acute monocytic leukemia cells (THP-1). Objective: Macrophage alternative activation, TGF-¦Â1 and epithelial-mesenchymal transition (EMT) are intensively involved in pulmonary fibrosis. Recent studies demonstrated that Apo A-I resolved established pulmonary fibrotic nodules, and D-4F inhibited TGF-¦Â1 induced EMT in alveolar cells. Therefore, this study evaluated the effects of D-4F on IL-4 induced macrophage alternative activation and TGF-¦Â1 expression. Materials and methods: THP-1 cells were simulated with PMA (100£¿ng/mL) for 48£¿h and treated with medium control, IL-4 (20£¿ng/mL) alone, or IL-4 (20£¿ng/mL) in the presence of D-4F (1, 5, and 10£¿¦Ìg/mL) for 24 and 48£¿h. Flow cytometry, RT-PCR and ELISA evaluations were performed to investigate the subsequent effects of D-4F. Results: Compared to stimulation with IL-4 alone, 1, 5, and 10£¿¦Ìg/mL of D-4F reduced alternative activation by 45.38%, 59.98%, and 60.10%, increased TNF-¦Á mRNA levels by 8%, 11%, and 16% and decreased TGF-¦Â1 mRNA levels by 21%, 37%, and 39%, respectively (all p£¿¡Ü£¿0.05). In addition, TNF-¦Á protein levels increased from 388£¿pg/mL (IL-4 alone) to 429, 475, and 487£¿pg/mL (1, 5, and 10£¿¦Ìg/mL D-4F), while TGF-¦Â1 protein levels dropped from 27.01£¿pg/mL (IL-4 alone) to 19.15, 12.27, and 10.47£¿pg/mL (1, 5, and 10£¿¦Ìg/mL D-4F). Conclusion: D-4F suppressed IL-4 induced macrophage alternative activation and pro-fibrotic TGF-¦Â1 expression
%U https://www.tandfonline.com/doi/full/10.1080/13880209.2019.1640747