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PM 2.5 Exposure Inhibits Transepithelial Anion Short-circuit Current by Downregulating P2Y2 Receptor/CFTR Pathway.
- Source :
-
International journal of medical sciences [Int J Med Sci] 2024 Jul 22; Vol. 21 (10), pp. 1929-1944. Date of Electronic Publication: 2024 Jul 22 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- Fine particulate matter (PM <subscript>2.5</subscript> ) can damage airway epithelial barriers. The anion transport system plays a crucial role in airway epithelial barriers. However, the detrimental effect and mechanism of PM <subscript>2.5</subscript> on the anion transport system are still unclear. In this study, airway epithelial cells and ovalbumin (OVA)-induced asthmatic mice were used. In transwell model, the adenosine triphosphate (ATP)-induced transepithelial anion short-circuit current (I <subscript>sc</subscript> ) and airway surface liquid (ASL) significantly decreased after PM <subscript>2.5</subscript> exposure. In addition, PM <subscript>2.5</subscript> exposure decreased the expression levels of P2Y2R, CFTR and cytoplasmic free-calcium, but ATP can increase the expressions of these proteins. PM <subscript>2.5</subscript> exposure increased the levels of Th2-related cytokines of bronchoalveolar lavage fluid, lung inflammation, collagen deposition and hyperplasisa of goblet cells. Interestingly, the administration of ATP showed an inhibitory effect on lung inflammation induced by PM <subscript>2.5</subscript> . Together, our study reveals that PM <subscript>2.5</subscript> impairs the ATP-induced transepithelial anion I <subscript>sc</subscript> through downregulating P2Y2R/CFTR pathway, and this process may participate in aggravating airway hyperresponsiveness and airway inflammation. These findings may provide important insights on PM <subscript>2.5</subscript> -mediated airway epithelial injury.<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.<br /> (© The author(s).)
- Subjects :
- Animals
Mice
Humans
Adenosine Triphosphate metabolism
Ovalbumin immunology
Signal Transduction drug effects
Epithelial Cells drug effects
Epithelial Cells metabolism
Down-Regulation drug effects
Respiratory Mucosa metabolism
Respiratory Mucosa drug effects
Respiratory Mucosa pathology
Bronchoalveolar Lavage Fluid cytology
Bronchoalveolar Lavage Fluid chemistry
Bronchoalveolar Lavage Fluid immunology
Receptors, Purinergic P2Y2 metabolism
Receptors, Purinergic P2Y2 genetics
Asthma metabolism
Asthma pathology
Asthma drug therapy
Asthma chemically induced
Asthma immunology
Particulate Matter adverse effects
Particulate Matter toxicity
Cystic Fibrosis Transmembrane Conductance Regulator metabolism
Cystic Fibrosis Transmembrane Conductance Regulator genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1449-1907
- Volume :
- 21
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- International journal of medical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39113893
- Full Text :
- https://doi.org/10.7150/ijms.96777