The protective effects of granulocyte-macrophage colony-stimulating factor against radiation-induced lung injury

Abstract

Background: Radiation-induced lung injury (RILI) is a common complication of thoracic cancer radiation therapy. Currently, there is no effective treatment for RILI. RILI is associated with chronic inflammation, this injury is perpetuated by the stimulation of chemokines and proinflammatory cytokines. Recent studies have demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a pivotal role in inflammation and fibrosis. This study aimed to investigate the protective effect of GM-CSF against the development of RILI in lung tissue.Method: First, a single fraction of radiation at a dose of 16 Gy was targeted at the entire thorax of wild-type (WT) C57BL/6 mice and GM-CSF -/mice to induce RILI. Second, we detected the radioprotective effects of GM-CSF by measuring the inflammatory biomarkers and fibrosis alteration on radiated lung tissues. Furthermore, we investigated the potential mechanism of GM-CSF protective effects in RILI. Results:The GM-CSF -/mice sustained more severe RILI than the WT mice. RILI was significantly alleviated by GM-CSF treatment. Intraperitoneally administered GM-CSF significantly inhibited inflammatory cytokine production and decreased epithelial-mesenchymal transition (EMT) in the RILI mouse model. Conclusions: GM-CSF was shown to be an important modulator of RILI through regulating inflammatory cytokines, which provides a new strategy for the prevention and treatment of RILI.

METTL3 Mediates Epithelial–Mesenchymal Transition by Modulating FOXO1 mRNA N6‐Methyladenosine‐Dependent YTHDF2 Binding: A Novel Mechanism of Radiation‐Induced Lung Injury

“…Serum profibrotic cytokines are closely associated with the occurrence of pulmonary fibrosis. [19] In the present study, the AAV9-shMETTL3 treatment significantly decreased the serum levels of proinflammatory and profibrotic cytokines in irradiated C57BL/6 mice compared with those in vehicle-treated control mice (Figure 4K). The infiltration of macrophages and neutrophils in lung tissues is an important pathological feature of RILI.…”

Intramuscular injection of skeletal muscle derived extracellular matrix mitigates denervation atrophy after sciatic nerve transection

“…In the canonical PI3K/AKT/IGF-1 pathway, binding of IGF-1 excreted from damaged myoblasts activates AKT phosphorylation for continued protein synthesis from myofibers while limiting lipogenesis, 63 possibly causing the discrepancies in lipid accumulations of the skECM conditions. GM-CSF has also been shown as an antifibrotic cytokine, 64 , 65 perhaps contributing to the lessened collagenous deposition as shown in the Masson’s Trichrome imaging of the d-skECM relative to Control and p-skECM ( Figure 7 ). Injections of skECM resulted in significantly higher expression of VEGF relative to the Control cohort.…”

Emetine dihydrochloride alleviated radiation‐induced lung injury through inhibiting EMT

“…EMT is thought to play critical roles in RILI. 10 It is characterized of RILI, 11 while mesenchymal stem cell therapy, 3 macrophage colony-stimulating factor, 12 Polydatin, 13 Heat-killed Salmonella typhimurium, 9 Grape seed pro-anthocyanidins 14 and so on can produce certain prevention and treatment effects by regulating EMT.…”