Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
Institute of Respiratory Diseases of Sun Yat-Sen University, Guangzhou, Guangdong, China.
Immun Inflamm Dis. 2023 May;11(5):e847. doi: 10.1002/iid3.847.
The link between colony-stimulating factor 1 (CSF1) and asthma was reported recently. However, the role and mechanism of CSF1 in asthma remain poorly understood. In this study, we aimed to explore the expression and its potential mechanism of CSF1 in asthma.
CSF1 expression in the airway samples from asthmatics and healthy controls were examined, then the correlations between CSF1 and eosinophilic indicators were analyzed. Subsequently, bronchial epithelial cells (BEAS-2B) with CSF1 overexpression and knockdown were constructed to investigate the potential molecular mechanism of CSF1. Finally, the effect of CSF1R inhibitor on STAT1 was investigated.
The expression of CSF1 was significantly increased in patients with asthma compared to healthy controls, especially in patients with severe and eosinophilic asthma. Upregulated CSF1 positively correlated with airway-increased eosinophil inflammation. In vitro, cytokines interleukin 13 (IL-13) and IL-33 can stimulate the upregulation of CSF1 expression. CSF1 overexpression enhanced p-CSF1R/CSF1R and p-STAT1/STAT1 expression, while knockdown CSF1 using anti-CSF1 siRNAs decreased p-CSF1R/CSF1R and p-STAT1/STAT1 expression. Furthermore, the inhibitor of CSF1R significantly decreased p-STAT1/STAT1 expression.
Sputum CSF1 may be involved in asthmatic airway eosinophil inflammation by interacting with CSF1R and further activating the STAT1 signaling. Interfering this potential pathway could serve as an anti-inflammatory therapy for asthma.
最近有报道称集落刺激因子 1（CSF1）与哮喘之间存在关联。然而，CSF1 在哮喘中的作用和机制仍知之甚少。在这项研究中，我们旨在探索 CSF1 在哮喘中的表达及其潜在机制。
检测哮喘患者和健康对照者气道样本中的 CSF1 表达，并分析 CSF1 与嗜酸性粒细胞指标之间的相关性。随后，构建 CSF1 过表达和敲低的支气管上皮细胞（BEAS-2B），以研究 CSF1 的潜在分子机制。最后，研究 CSF1R 抑制剂对 STAT1 的影响。
与健康对照组相比，哮喘患者的 CSF1 表达明显增加，尤其是在严重和嗜酸性粒细胞性哮喘患者中。上调的 CSF1 与气道嗜酸性粒细胞炎症增加呈正相关。在体外，细胞因子白细胞介素 13（IL-13）和 IL-33 可刺激 CSF1 表达上调。CSF1 过表达增强了 p-CSF1R/CSF1R 和 p-STAT1/STAT1 的表达，而使用抗 CSF1 siRNA 敲低 CSF1 则降低了 p-CSF1R/CSF1R 和 p-STAT1/STAT1 的表达。此外，CSF1R 的抑制剂显著降低了 p-STAT1/STAT1 的表达。
痰 CSF1 可能通过与 CSF1R 相互作用并进一步激活 STAT1 信号通路，参与哮喘气道嗜酸性粒细胞炎症。干扰这一潜在通路可能成为哮喘的一种抗炎治疗方法。
