Exposure interval to ambient fine particulate matter (PM2.5) collected in Southwest China induced pulmonary damage through the Janus tyrosine protein kinase‐2/signal transducer and activator of transcription‐3 signaling pathway both in vivo and in vitro

• Published in: Journal of applied toxicology Vol. 41; no. 12; pp. 2042 - 2054
• Main Authors: Yue, Wuyang, Chen, Xuxi, He, Sifu, Li, Na, Zhang, Lishi, Chen, Jinyao
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.12.2021
• Subjects: A549 Cells; Air Pollutants - toxicity; Air pollution; animal test; Animals; Apoptosis; Biocompatibility; Cell activation; Cell cycle; China; Chronic obstructive pulmonary disease; Fibrosis; Flow cytometry; Growth factors; Health risks; Humans; Immunohistochemistry; In vivo methods and tests; Inflammation; Inflammatory response; Injuries; JAK‐2/STAT‐3 signaling pathway; Janus kinase; Janus Kinase 2 - genetics; Janus Kinase 2 - metabolism; Kinases; Lung cancer; Lung diseases; lung injury; Male; Nanoparticles; Obstructive lung disease; Particulate matter; Particulate Matter - toxicity; PM2.5; Pollutants; Protein kinase; Proteins; Public health; Pulmonary functions; Rats; Rats, Sprague-Dawley; Respiratory function; Serum levels; Signal transduction; Signal Transduction - drug effects; Signaling; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Trachea; Transcription; Tyrosine; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; China; A549 cells; lung injury; JAK-2/STAT-3 signaling pathway; PM2.5; animal test
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.4196

PM2.5 is a well‐known air pollutant threatening public health. Studies confirmed that exposure to the particles could impair pulmonary function, cause chronic obstructive pulmonary disease, and increase the incidence of lung cancer. The characteristic of PM2.5 varies across regions. The toxic function of PM2.5 in southwest China remains to be elucidated. This study aimed to investigate lung injury and its mechanisms induced by PM2.5 collected in Chengdu. Rats were administered with PM2.5 by intratracheal instillation for 4 weeks. Biochemical, cell count, and inflammation‐related parameters were measured. Lung tissues were obtained for hematoxylin and eosin and Masson's trichrome staining. The expression levels of vascular endothelial growth factor (VEGF), Janus tyrosine protein kinase‐2 (JAK‐2), and signal transducer and activator of transcription‐3 (STAT‐3) were detected by immunohistochemistry assays. Meanwhile, A549 cells were treated with the PM2.5. The cell cycle, and apoptosis were measured by flow cytometry. mRNA and protein expressions of JAK‐2, STAT‐3, p‐STAT‐3, and VEGFA were detected using qPCR and Western blot analysis respectively. Results of in vivo study showed that PM2.5 induced lung pathological injury, aggravated the accumulation of inflammatory cells, and increased the serum levels of inflammatory factors. In vitro experiments showed that PM2.5 disrupted the cell growth cycle and increased cell apoptosis through the activation of the JAK‐2/STAT‐3 signaling pathway. Taken together, this study provided convincing experimental evidence that PM2.5 collected in southwest China could induce pulmonary injury as manifested by inflammatory response and lung fibrosis, possibly through the modulation of the JAK‐2/STAT‐3 signaling pathway. Lung injury to inhaled PM2.5 was assessed by Western blot analysis in tandem with flow cytometry and hematoxylin and eosin staining. Our results highlight the adverse effects of the PM2.5 collected in Southwest China to induce inflammatory responses, cell cycle arrest, and cell apoptosis depending on the activation of the JAK‐2/STAT‐3 signaling pathway.