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Published on: January 19, 2019
Molecular pathways of radiation-induced lung damage: Effects of X-ray and Anti-PD-1 combination in a murine model
Chenglong Sun1, Yang Zhang2, Jinfeng Liu2
1Department of Radiotherapy, Anhui No.2 Provincial People's Hospital Clinical College, Anhui Medical University, Hefei, Anhui 230041, PR China; Department of Radiotherapy, Anhui No.2 Provincial People's Hospital, Hefei, Anhui 230041, PR China.
Objective:
To clarify the impact of X-ray irradiation combined with PD-1 immune checkpoint inhibitor treatment on lung tissue in a mouse model of radiation-induced lung injury (RILI) and to investigate its underlying mechanisms.
Methods:
A mouse RILI model was established by a single 16 Gy dose of whole-thorax irradiation. Mice were then treated with either an PD-1 inhibitor or a control. Lung injury and fibrosis were assessed by histological staining. Inflammatory cytokine levels (TNF-α, IL-6) were measured by ELISA. Macrophage M1 polarization was analyzed by flow cytometry and immunohistochemistry. The activation of the NF-κB signaling pathway was evaluated by Western blot.
Results:
The lung injury indices in the group treated with irradiation combined with PD-1 inhibitor were higher than those in the irradiation-only group. Mechanistic studies found that PD-1 inhibitors promoted the activation of the NF-κB signaling pathway and simultaneously regulated macrophage polarization in lung tissue, promoting the differentiation of M1-type pro-inflammatory cells.
Conclusion:
Whole-thorax X-ray irradiation combined with PD-1 inhibitors can exacerbate lung injury and pulmonary fibrosis in mice, and the mechanism of action may be through the regulation of NF-κB signaling pathway activation to promote macrophage polarization towards the M1 type.
