Glycyrrhetinic Acid Mitigates Radiation-Induced Pulmonary Fibrosis via Inhibiting the Secretion of TGF-ß1 by Treg Cells.

PURPOSE: 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. METHODS AND MATERIALS: 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-ß1 (TGF-ß1) inhibitor to block TGF-ß1 was conducted to study the mechanism by which GA alleviates RIPF. Furthermore, injection of Treg cells into GA-treated RIPF mice to upregulate TGF-ß1 levels was performed to verify the roles of TGF-ß1 and Treg cells. RESULTS: GA intervention improved the damage to lung tissue structure and collagen deposition and inhibited Treg cell infiltration, TGF-ß1 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-ß1 inhibitor, by decreasing TGF-ß1. Furthermore, reinfusion of Treg cells upregulated TGF-ß1 levels and exacerbated RIPF in GA-treated RIPF mice. CONCLUSIONS: GA can improve RIPF in mice, and the corresponding mechanisms may be related to the inhibition of TGF-ß1 secreted by Treg cells to induce EMT and MFB transformation. Therefore, GA may be a promising therapeutic candidate for the clinical treatment of RIPF.

A Subset of Breg Cells, B10, Contributes to the Development of Radiation-Induced Pulmonary Fibrosis.

PURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a serious side effect of radiation therapy, but the underlying mechanisms are unknown. B10 cells, as negative B regulatory cells, play important roles in regulating inflammation and autoimmunity. However, the role of B10 cells in RIPF progression is unclear. The aim of this study was to determine the role of B10 cells in aggravating RIPF and the underlying mechanism. METHODS AND MATERIALS: The role of B10 cells in RIPF was studied by constructing mouse models of RIPF and depleting B10 cells with an anti-CD22 antibody. The mechanism of B10 cells in RIPF was further explored through cocultivation of B10 cells and MLE-12 or NIH3T3 cells and administration of an interleukin (IL)-10 antibody to block IL-10. RESULTS: B10 cell numbers increased significantly during the early stage in the RIPF mouse models compared with the controls. In addition, depleting B10 cells with the anti-CD22 antibody attenuated the development of lung fibrosis in mice. Subsequently, we confirmed that B10 cells induced epithelial-mesenchymal transition and the transformation of myofibroblasts via activation of STAT3 signaling in vitro. After blockade of IL-10, it was verified that IL-10 secreted by B10 cells mediates the epithelial-mesenchymal transition of myofibroblasts, thereby promoting RIPF. CONCLUSIONS: Our study uncovers a novel role for IL-10-secreting B10 cells that could be a new target of research for relieving RIPF.

Prognostic Value of Serum Transferrin Level before Radiotherapy on Radio-Sensitivity and Survival in Patients with Nasopharyngeal Carcinoma.

PURPOSE: To investigate the prognostic value of serum transferrin (TRF) level before intensity-modulated radiation therapy (IMRT) on radio-sensitivity and overall survival (OS) in patients with nasopharyngeal carcinoma (NPC). METHODS: From October 2012 to October 2016, a total of 348 patients with NPC in the First Affiliated Hospital of Fujian Medical University were retrospectively analyzed in our study. The concentration of serum TRF was detected by the method of enzyme-linked immunosorbent assay (ELISA). In the whole group, 46 patients received IMRT, and 302 patients received IMRT plus chemotherapy. The radio-sensitive tumor was defined when the local tumor lesions disappeared completely in the nasopharyngeal MRI scan and no tumor residues were found under the electronic nasopharyngoscope one month after the end of radiotherapy. RESULTS: The serum TRF level before IMRT was (1.34-3.89) g/L, with a median of 2.16 g/L and a mean of (2.20 ± 0.42) g/L. In the whole group, 242 cases (69.5%) were radiosensitive, and 106 cases (30.5%) were insensitive. The number of radiosensitive patients in the group of HTRF (transferrin > 2.16 g/L) and LTRF (transferrin ≤ 2.16 g/L) before radiotherapy was 129 (74.6%) and 113 (64.6%), respectively. The difference in radio-sensitivity between the two groups was statistically significant (χ2 = 4.103, p = 0.043). Logistic regression analysis showed that the level of TRF before radiotherapy (OR = 1.702; 95% CI 1.044~2.775; p = 0.033) was an independent factor for radio-sensitivity. The log-rank test showed that patients in the LTRF group achieved a significantly worse OS (χ2 = 5.388, p = 0.02) than those in the HTRF group. Cox regression analysis showed that baseline TRF level (HR = 1.706; 95% CI 1.065~2.731; p = 0.026) was an independent prognostic factor for overall survival. CONCLUSIONS: The low level of TRF before IMRT is a risk factor for radio-sensitivity and a prognostic factor for poor OS in NPC patients. It may be a promising marker to predict radio-sensitivity and OS in NPC patients who accept IMRT.