Respiratory medicine · 2025
Diesel exhaust particles exaggerate chronic intermittent hypoxia-induced lung neutrophil infiltration through CXCL5 and CCL5 in mice.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Sun Yipeng, Zhang Mengzhe, Li Shanqun, Huang Huai, Wu Xiaodan
Аннотация
BACKGROUND: Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH) and subsequent respiratory tract inflammation. While air pollution is identified as an OSA risk factor and can influence disease severity, its specific pulmonary effects and underlying mechanisms remain unclear.
METHODS: We established a murine model of OSA in C57BL/6 mice using 5-week CIH, with and without 2-day diesel exhaust particle (DEP) exposure and used 16HBE bronchial epithelial cells in vitro. We conducted RNA sequencing on lung tissues to analyse gene expression and utilized hematoxylin and eosin (HE) staining to assess mice lung inflammation. Additionally, immunohistochemistry was performed to evaluate protein expression levels. Chemokines in bronchoalveolar lavage fluid (BALF) were identified using a panel, followed by ELISA quantification.
RESULTS: Compared with the control group, CIH resulted in heightened lung inflammation, increased BALF protein concentrations, and elevated expression of hypoxia-related genes. The CIH + DEP group exhibited even more pronounced elevations in these indicators. RNA sequencing identified that CIH upregulated neutrophil-related cytokine genes in lung tissue. Specifically, DEP amplified this upregulation. Furthermore, myeloperoxidase expression, indicative of neutrophil activation, significantly increased in the lung tissue and BALF of the CIH group. The CIH + DEP group showed an even more substantial rise. Subsequent protein screening and ELISA confirmed marked elevations of CXCL5 and CCL5 in both CIH and DEP groups. In 16HBE cells, DEP aggravated CIH-induced secretion of CXCL5 and CCL5, and p-p38 protein expression, which was ameliorated by the p38 MAPK inhibitor SB 203580.
CONCLUSION: DEP aggravated CIH-induced lung inflammation and neutrophil infiltration, which was likely mediated by CXCL5 and CCL5.
METHODS: We established a murine model of OSA in C57BL/6 mice using 5-week CIH, with and without 2-day diesel exhaust particle (DEP) exposure and used 16HBE bronchial epithelial cells in vitro. We conducted RNA sequencing on lung tissues to analyse gene expression and utilized hematoxylin and eosin (HE) staining to assess mice lung inflammation. Additionally, immunohistochemistry was performed to evaluate protein expression levels. Chemokines in bronchoalveolar lavage fluid (BALF) were identified using a panel, followed by ELISA quantification.
RESULTS: Compared with the control group, CIH resulted in heightened lung inflammation, increased BALF protein concentrations, and elevated expression of hypoxia-related genes. The CIH + DEP group exhibited even more pronounced elevations in these indicators. RNA sequencing identified that CIH upregulated neutrophil-related cytokine genes in lung tissue. Specifically, DEP amplified this upregulation. Furthermore, myeloperoxidase expression, indicative of neutrophil activation, significantly increased in the lung tissue and BALF of the CIH group. The CIH + DEP group showed an even more substantial rise. Subsequent protein screening and ELISA confirmed marked elevations of CXCL5 and CCL5 in both CIH and DEP groups. In 16HBE cells, DEP aggravated CIH-induced secretion of CXCL5 and CCL5, and p-p38 protein expression, which was ameliorated by the p38 MAPK inhibitor SB 203580.
CONCLUSION: DEP aggravated CIH-induced lung inflammation and neutrophil infiltration, which was likely mediated by CXCL5 and CCL5.