Wood Smoke Particles Stimulate MUC5AC Overproduction by Human Bronchial Epithelial Cells Through TRPA1 and EGFR Signaling

• DOI: 10.1093/toxsci/kfaa006
• Publication Date: 2020-01-10T20:10:32Z
• Authors: Tosifa A Memon; Nam D Nguyen; Katherine L Burrell; Abigail F Scott; Marysol Almestica...; Emmanuel Rapp; Cassandra E Deeri...; Christopher A Reilly
• Keywords: 0301 basic medicine; Inhalation Exposure; Glycogen Synthase Kinase 3 beta; Bronchi; Epithelial Cells; Mucin 5AC; Wood; p38 Mitogen-Activated Protein Kinases; Up-Regulation; 3. Good health; ErbB Receptors; Mice, Inbred C57BL; 03 medical and health sciences; 13. Climate action; Smoke; 11. Sustainability; Animals; Humans; TRPA1 Cation Channel; Cells, Cultured; Signal Transduction

Abstract Mucus hypersecretion is a pathological feature of acute inflammatory and chronic obstructive pulmonary diseases. Exposure to air pollutants can be cause mucus overproduction, but mechanisms by which different forms elicit this response are not fully understood. In study, particulate matter (PM) generated from burning pine wood other types biomass was used determine these PM stimulate mucin gene expression secretion primary human bronchial epithelial cells (HBECs). Biomass < 2.5 μm several fuels stimulated the gel-forming glycoprotein MUC5AC HBECs. Muc5ac induction also observed in mouse airways following subacute oropharyngeal delivery smoke PM. HBECs, induced transient receptor potential ankyrin-1 (TRPA1) agonists’ coniferaldehyde, component PM, allyl isothiocyanate, attenuated TRPA1 antagonist. Additionally, inhibition epidermal growth factor (EGFR/ErbB1) EGFR signaling partners p38 MAPK GSK3β prevented overexpression. Collectively, our results suggest that activation EGFR, paired with alterations activity, plays major role overproduction exposed These reveal specific processes for how may impact respiratory system highlight avenues therapeutic manipulation lung diseases affected pollutants.