Dihydroartemisinin Attenuates Radiation-Induced Lung Injury by Inhibiting the cGAS/STING/NF-κB Signaling Pathway

Area of Science:

• Biomedical Science
• Radiotherapy Research
• Inflammation and Immunology

Background:

• Dihydroartemisinin (DHA), a derivative of artemisinin, influences inflammation, oxidative stress, and immune responses.
• The precise mechanisms behind DHA's therapeutic effects, particularly in radiation-induced lung injury (RILI), are not fully understood.
• Understanding these mechanisms is crucial for improving lung radiotherapy outcomes.

Purpose of the Study:

• To investigate the underlying mechanism of Dihydroartemisinin (DHA) in mitigating radiation-induced lung injury (RILI).
• To explore the role of the cGAS-STING signaling pathway in RILI and DHA's potential modulation of this pathway.
• To identify potential therapeutic targets for RILI within the elucidated signaling cascade.

Main Methods:

• Utilized a mouse model (C57BL/6J) subjected to whole chest irradiation (15 Gy) to induce RILI.
• Assessed RILI through qRT-PCR, ELISA, histology, Western blot, and immunohistochemistry.
• Employed small interfering RNA (siRNA) to knockdown cGAS in BEAS-2B cells (human bronchial epithelium) for in vitro validation.

Main Results:

• Irradiation activated the cGAS-STING pathway, leading to NF-κB phosphorylation and increased inflammatory factors in both mouse and cell models.
• Knockdown of cGAS using siRNA significantly attenuated RILI in the BEAS-2B cell model.
• Dihydroartemisinin (DHA) demonstrated a protective effect by modulating the cGAS/STING/NF-κB signaling pathway.

Conclusions:

• The study elucidates Dihydroartemisinin's (DHA) mechanism in reducing RILI via the cGAS/STING/NF-κB signaling pathway.
• The cGAS/STING/NF-κB axis represents a promising therapeutic target for managing radiation-induced lung injury.
• Findings provide novel insights into mitigating lung damage during radiotherapy.