Abstract
The proliferation of fetal alveolar type II cells (FATIICs) was impaired in bronchopulmonary dysplasia (BPD), which is modulated by hyperoxia and inflammatory response. Interleukin 24 (IL-24), a cytokine produced by certain cell types, plays an essential role in inflammation and host protection against infection. However, the ability of FATIICs to produce IL-24 remains unclear, and the role of IL-24 in BPD progression is yet to be determined. With reverse transcription quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay, the authors evaluated whether FATIICs produce IL-24 in physiological conditions. The authors quantified IL-24 expression in the lungs of newborn rat pups exposed to hyperoxia (70% oxygen) and in FATIICs isolated on embryonic day 19 that were exposed to 95% oxygen or lipopolysaccharide (LPS). The role of IL-24 in FATIICs, cell proliferation, cell apoptosis, and cell cycle were further evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometric analysis. Also, they assessed caspase-3 and SOCS3 mRNA in IL-24 siRNA-treated cells by using RT-qPCR. During culture, IL-24 mRNA and protein levels in FATIICs gradually decreased with FATIIC differentiation. IL-24 expression increased significantly in rat lungs exposed to hyperoxia and FATIICs exposed to oxygen or LPS. Recombinant IL-24 enhanced cell proliferation by decreasing the proportion of apoptotic cells and increasing the proportion of cells in the S phase. The IL-24 siRNA-treated cells expressed more caspase-3 mRNA. Furthermore, suppressor of cytokine signaling 3 (SOCS3) mRNA was significantly decreased in rats and FATIICs exposed to oxygen, whereas it dramatically increased in FATIICs exposed to LPS. The IL-24 siRNA-treated cells expressed more SOCS3 mRNA. These studies suggest IL-24 is a pulmonary target cytokine in BPD, and may possibly regulate SOCS3 in oxidative stress and inflammation of the lung.
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Acknowledgements
This work was financially supported by the key scientific and technological project of the Chinese Ministry of Education (grant no. 212103). The experiment of the expression of IL-24 in lungs exposed to hyperoxia and FATIICs exposed to oxygen and LPS was conducted at the Children’s Hospital of Fudan University. The experiment on the role of IL-24 in FATIIC development was conducted in Binzhou Medical University Hospital.
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Gao, R., Li, Z., Ai, D. et al. Interleukin-24 as a Pulmonary Target Cytokine in Bronchopulmonary Dysplasia. Cell Biochem Biophys 79, 311–320 (2021). https://doi.org/10.1007/s12013-021-00968-z
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DOI: https://doi.org/10.1007/s12013-021-00968-z