Aspirin-Triggered Resolvin D1 Reduces Chronic Dust-Induced Lung Pathology without Altering Susceptibility to Dust-Enhanced Carcinogenesis

Cancers

Tara M. Nordgren¹  Rattapol Phandthong²  Stephanie Guardado³  Stefanie Sveiven³  Arzu Ulu³  Matthew Nguyen³  Prue Talbot⁴  Edward C. Dominguez⁴ 

[1] Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA;Department of Molecular, Cell and Systems Biology, University of California Riverside, Riverside, CA 92521, USA;Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, CA 92521, USA;Environmental Toxicology Graduate Program, University of California Riverside, Riverside, CA 92521, USA;

关键词: lung inflammation;    lung cancer;    omega-3 fatty acids;    specialized pro-resolving mediators (SPM);    organic dust;    epithelial to mesenchymal transition (EMT);   

DOI  :  10.3390/cancers14081900

来源: DOAJ

【 摘 要 】

Lung cancer is the leading cause of cancer-related deaths worldwide, with increased risk being associated with unresolved or chronic inflammation. Agricultural and livestock workers endure significant exposure to agricultural dusts on a routine basis; however, the chronic inflammatory and carcinogenic effects of these dust exposure is unclear. We have developed a chronic dust exposure model of lung carcinogenesis in which mice were intranasally challenged three times a week for 24 weeks, using an aqueous dust extract (HDE) made from dust collected in swine confinement facilities. We also treated mice with the omega-3-fatty acid lipid mediator, aspirin-triggered resolvin D1 (AT-RvD1) to provide a novel therapeutic strategy for mitigating the inflammatory and carcinogenic effects of HDE. Exposure to HDE resulted in significant immune cell influx into the lungs, enhanced lung tumorigenesis, severe tissue pathogenesis, and a pro-inflammatory and carcinogenic gene signature, relative to saline-exposed mice. AT-RvD1 treatment mitigated the dust-induced inflammatory response but did not protect against HDE + NNK-enhanced tumorigenesis. Our data suggest that chronic HDE exposure induces a significant inflammatory and pro-carcinogenic response, whereas treatment with AT-RvD1 dampens the inflammatory responses, providing a strong argument for the therapeutic use of AT-RvD1 to mitigate chronic inflammation.

【 授权许可】

Unknown