Spleen tyrosine kinase inhibition mitigates radiation-induced lung injury through anti-inflammatory effects and downregulation of p38 MAPK and p53

To explore new modulatory intervention targets for radiation-induced lung injury, bioinformatics analysis technology was used to search for the core driving genes in the pathogenesis of radiation pneumonitis, and the

Syk inhibitor may have a potential to be used as a targeted drug to mitigate radiation pneumonitis and inhibit radiation-induced pulmonary fibrosis.

We screened Syk as one of the most important driver genes of radiation pneumonitis by bioinformatics analysis and screened the preferred Syk inhibitor fostamatinib from the drug database. Syk was highly expressed in irradiated lung tissue, and fostamatinib inhibited the level of Syk expression. Syk inhibitor significantly alleviated the radiation-induced lung injury and downregulated the increased expression of p38 MAPK, p53, IL-1β, and IL-6 in lung tissue at 2 weeks after radiation. The levels of TGF-β, COL1A1, and α-SMA and degree of pulmonary fibrosis at 10 weeks after radiation were also decreased by Syk inhibitor.