Serum amyloid A contributes to radiation-induced lung injury by activating macrophages through FPR2/Rac1/NF-κB pathway.

Autor:	Liu X; Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China.; Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China., Song Y; Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China., Hu S; Department of Preventive Dentistry, Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital & School of Stomatology, Shanghai Medical College, Fudan University, Shanghai 200001, China., Bai Y; Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China., Zhang J; Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China., Tai G; Department of Radiotherapy, Nantong Tumor Hospital and the Affiliated Tumor Hospital of Nantong University, Nantong 226631, Jiangsu Province, China., Shao C; Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China., Pan Y; Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Jazyk:	angličtina
Zdroj:	International journal of biological sciences [Int J Biol Sci] 2024 Sep 16; Vol. 20 (12), pp. 4941-4956. Date of Electronic Publication: 2024 Sep 16 (Print Publication: 2024).
DOI:	10.7150/ijbs.100823
Abstrakt:	Patients who receive thoracic radiotherapy may suffer from radiation-induced lung injury, but the treatment options are limited as the underlying mechanisms are unclear. Using a mouse model of right thorax irradiation with fractionated doses of X-rays for three consecutive days (8 Gy/per day), this study found that the thoracic irradiation (Th-IR) induced tissue injury with aberrant infiltration of macrophages, and it significantly increased the secretion of TNF-α, IL-1β, IL-6, TGF-β1 and serum amyloid A (SAA) in mice. Interestingly, SAA could activate macrophages and then induce epithelial-mesenchymal transition (EMT) of lung epithelial cells and fibrosis progression in lung tissue. Mechanistically, SAA enhanced the transient binding of FPR2 to Rac1 protein and further activated NF-κB signaling pathway in macrophages. Inhibition of FPR2 significantly reduced pulmonary fibrosis induced by SAA administration in mice. In addition, cimetidine could reduce the level of SAA release after irradiation and attenuate the lung injury induced by SAA or Th-IR. In conclusion, our results demonstrated that SAA activated macrophages via FPR2/Rac1/NF-κB pathway and might contribute to the Th-IR induced lung injury, which may provide a new strategy to attenuate radiation-induced adverse effects during radiotherapy. Competing Interests: Competing Interests: The authors have declared that no competing interest exists. (© The author(s).)
Databáze:	MEDLINE
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