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

Publisher: Ivyspring International Country of Publication: Australia NLM ID: 101235568 Publication Model: eCollection Cited Medium: Internet ISSN: 1449-2288 (Electronic) Linking ISSN: 14492288 NLM ISO Abbreviation: Int J Biol Sci Subsets: MEDLINE

Original Publication: Lake Haven, N.S.W., Australia : Ivyspring International, c2004-

Serum Amyloid A Protein*/metabolism ; NF-kappa B*/metabolism ; Receptors, Formyl Peptide*/metabolism ; Lung Injury*/metabolism ; Lung Injury*/etiology ; rac1 GTP-Binding Protein*/metabolism ; Macrophages*/metabolism ; Macrophages*/radiation effects ; Signal Transduction*; Animals ; Mice ; Mice, Inbred C57BL ; Male ; Receptors, Lipoxin/metabolism ; Epithelial-Mesenchymal Transition/radiation effects ; Radiation Injuries/metabolism ; Radiation Injuries/pathology ; Neuropeptides

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).)

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Keywords: FPR2 and NF-κB; Lung injury; Macrophages; SAA; Thoracic irradiation

0 (Serum Amyloid A Protein)
0 (NF-kappa B)
0 (Receptors, Formyl Peptide)
EC 3.6.5.2 (rac1 GTP-Binding Protein)
0 (formyl peptide receptor 2, mouse)
0 (Receptors, Lipoxin)
0 (Rac1 protein, mouse)
0 (Neuropeptides)

Date Created: 20240923 Date Completed: 20240923 Latest Revision: 20240924

20240924

PMC11414394

10.7150/ijbs.100823

39309438