Glycyrrhetinic Acid Mitigates Radiation-Induced Pulmonary Fibrosis via Inhibiting the Secretion of TGF-β1 by Treg Cells

Abstract

Radiation-induced pulmonary fibrosis (RIPF) is a common side effect of radiation therapy for thoracic tumors without effective prevention and treatment methods at present. The aim of this study was to explore whether glycyrrhetinic acid (GA) has a protective effect on RIPF and the underlying mechanism. A RIPF mouse model administered GA was used to determine the effect of GA on RIPF. The cocultivation of regulatory T (Treg) cells with mouse lung epithelial-12 cells or mouse embryonic fibroblasts and intervention with GA or transforming growth factor-β1 (TGF-β1) inhibitor to block TGF-β1 was conducted to study the mechanism by which GA alleviates RIPF. Furthermore, injection of Treg cells into GA-treated RIPF mice to upregulate TGF-β1 levels was performed to verify the roles of TGF-β1 and Treg cells. GA intervention improved the damage to lung tissue structure and collagen deposition and inhibited Treg cell infiltration, TGF-β1 levels, epithelial mesenchymal transition (EMT), and myofibroblast (MFB) transformation in mice after irradiation. Treg cell-induced EMT and MFB transformation in vitro were prevented by GA, as well as a TGF-β1 inhibitor, by decreasing TGF-β1. Furthermore, reinfusion of Treg cells upregulated TGF-β1 levels and exacerbated RIPF in GA-treated RIPF mice. GA can improve RIPF in mice, and the corresponding mechanisms may be related to the inhibition of TGF-β1 secreted by Treg cells to induce EMT and MFB transformation. Therefore, GA may be a promising therapeutic candidate for the clinical treatment of RIPF.