Wen Yang Ding Chuan Tang Attenuates Asthmatic Airway Remodeling by Inhibiting M2 Macrophage-Driven Fibroblast Activation.

To study the effects of Wen Yang Ding Chuan Tang (WYDCT) on fibroblast function, airway remodeling in asthma, and the underlying mechanism. IL-4 was used to induce M2 polarization of RAW264.7 macrophages, and the polarized macrophages were then treated with WYDCT to investigate its effect on mouse lung fibroblasts. Polarized RAW264.7 cells were subjected to different treatments and then co-cultured with fibroblasts. M1 and M2 marker levels, cell morphology, and IL-6 concentration were assessed. STAT3 protein level was analyzed. Fibroblast viability, proliferation, colony formation, PCNA expression, and the expression of fibronectin, COL1A1, and α-SMA were analyzed using various assays, including real-time PCR, Western blot, CCK-8, Edu, immunofluorescence, and colony formation assays. WYDCT reversed the IL-4-induced morphological changes in RAW264.7 cells, reduced the levels of M2 markers (Arg-1, CD206) and IL-6, and decreased STAT3 expression in RAW264.7 cells, while supplementation with IL-6 restored the effect of WYDCT on M2 markers. Furthermore, WYDCT inhibited fibroblast viability and proliferation, reduced PCNA expression, and decreased fibrosis markers (fibronectin, COL1A1, α-SMA), suggesting that WYDCT inhibits the viability, proliferation, and fibrosis of lung fibroblasts by suppressing macrophage M2 polarization, in which the IL-6/STAT3 signaling pathway may play a key role.