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Effects of CpG Oligodeoxynucleotide 1826 on transforming growth factor-beta 1 and radiation-induced pulmonary
Xuan Li1, Guoxiong Xu2, Tiankui Qiao1
1Department of Radiation Oncology, Jinshan Hospital, Fudan University, Shanghai, China.
Background:
Cytosine-phosphate-guanine (CpG) oligodeoxyribonucleotides (ODNs) are synthetic DNA fragments containing unmethylated cytosine-guanine motifs with potential immune modulatory effects and have recently been suggested to enhance sensitivity to traditional therapies in lung cancer. This study aimed to examine the effects of CpG ODN1826 on transforming growth factor-beta 1(TGF-β1) and radiation-induced pulmonary fibrosis in mice.
Methods:
The radiation-induced pulmonary fibrosis mouse model was established by a single dose of 20 Gy, 6 MV X-rays exposure to the left lung. ICR mice were evenly randomized into four groups, comprising: a control group, a radiation group (RT group), a CpG group and a radiation combined with CpG ODN1826 group (RT + CpG group), with 40 mice in each group. CpG ODN1826 was intraperitoneally injected into mice at 1, 3, 5, 7 and 9 d post-irradiation. The mice were sacrificed at 1, 5, 15, 30 and 90 d post-irradiation. Paraffin sections of the radiated lung were subjected to H&E staining and Masson staining. The Ashcroft scale was used for quantitative histological analysis of fibrotic changes induced by irradiation. Concentrations of serum TGF-β1 were determined by ELISA, and concentrations of Hydroxyproline(Hyp) in the lung were determined with the alkaline hydrolysis method. Relative gene expression of FoxP3 was determined by real-time PCR.
Results:
The radiation-induced pulmonary fibrosis mouse model was successfully established. The serum concentrations of TGF -β1 of RT group were higher than those of the RT + CpG group (t = 5.212, 7.126, 7.972 and 3.785, P < 0.05). The Hyp in the lung of RT group was higher than that of RT + CpG group (t = 4.606, P < 0.05). The relative expressions of FoxP3 gene in the lung of the RT group were higher than those of RT + CpG group (t = 8.395, 5.099 and 6.147, P < 0.05).
Conclusions:
CpG ODN1826 could reduce the serum concentrations of TGF-β1 and the lung content of Hyp in radiation-induced pulmonary fibrosis, which might be related to the possibility that CpG ODN1826 can reduce expression of the FoxP3 gene.
Insights
CpG ODN1826 administration reduced transforming growth factor-beta 1 (TGF-β1) and hydroxyproline levels in radiation-induced pulmonary fibrosis. This suggests CpG ODN1826 may mitigate lung fibrosis by decreasing FoxP3 gene expression.
Area of Science:
- Immunology
- Oncology
- Pulmonary Medicine
Background:
- Cytosine-phosphate-guanine (CpG) oligodeoxyribonucleotides (ODNs) are synthetic DNA fragments with immune-modulatory potential.
- CpG ODNs have shown promise in enhancing sensitivity to lung cancer therapies.
- This study investigates CpG ODN1826's effect on radiation-induced pulmonary fibrosis.
Purpose of the Study:
- To evaluate the impact of CpG ODN1826 on transforming growth factor-beta 1 (TGF-β1) levels.
- To assess the efficacy of CpG ODN1826 in mitigating radiation-induced pulmonary fibrosis in a mouse model.
- To explore the relationship between CpG ODN1826, TGF-β1, and FoxP3 gene expression in pulmonary fibrosis.
Main Methods:
- Established a radiation-induced pulmonary fibrosis mouse model using 20 Gy X-rays.
- Administered CpG ODN1826 intraperitoneally to mice post-irradiation.
- Quantified serum TGF-β1, lung hydroxyproline (Hyp), and FoxP3 gene expression via ELISA, alkaline hydrolysis, and real-time PCR, respectively.
Main Results:
- CpG ODN1826 significantly reduced serum TGF-β1 concentrations compared to the radiation-only group.
- Lung hydroxyproline content was significantly lower in mice treated with CpG ODN1826.
- Relative FoxP3 gene expression in the lung was significantly decreased by CpG ODN1826 treatment.
Conclusions:
- CpG ODN1826 effectively reduces TGF-β1 and hydroxyproline levels in radiation-induced pulmonary fibrosis.
- The observed antifibrotic effects may be linked to CpG ODN1826's ability to downregulate FoxP3 gene expression.
- CpG ODN1826 shows potential as a therapeutic agent for mitigating radiation-induced lung damage.
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