House Dust Mite Exposure Transcriptionally Upregulates Amyloid Precursor Protein in Human Airway Epithelial Cells

Rationale: Asthma is characterized by airway inflammation and airway remodeling where the airway epithelium acts as both physical barrier and immune sensors. Epithelial cells are central in initiating the immune response and orchestrating inflammation during asthma. Amyloid precursor protein (APP) and its cleaved byproduct amyloid β are widely known for their role in neurodegeneration and contribute to barrier dysfunction and inflammation in Alzheimer’s disease. We recently reported that house dust mite (HDM) induced asthma potentiates Alzheimer’s disease changes in AppNL-G-F mice brain by increasing amyloid beta pathology, astrogliosis, microgliosis and cytokine changes. However, the effect of HDM on amyloid precursor protein expression in the structural cells of the lungs remains unexplored. Objective: This study aims to investigate the regulation of APP expression in airway epithelial cells following HDM exposure. Methods: Primary bronchial epithelial cells, isolated from bronchial brushing (collected at Sanford Broadway Clinic, Sanford IRB approved) and/or bronchial epithelial cell line (16HBE 14o-) were cultured in airway medium (Promocell) with supplements and AbAm. Cells were treated with 100 micrograms per ml (µg/mL) of HDM, and the expression of APP and beta secretase 1 (BACE1) were determined by RT-PCR, immunoblotting, and immunofluorescence. The APP promoter was analyzed to identify potential transcription factor binding motifs. Based on the number of binding sites four major transcription factors were selected and their expressions were determined by RT-PCR. To assess the promoter activity chromatin immunoprecipitation (ChIP) and luciferase reporter assay were performed on cells treated with HDM with pharmacological inhibitors or siRNA knockdown for functional validation. Results: HDM exposure significantly increased APP expression in airway epithelial cells at mRNA and protein levels. Along with APP, the expression of BACE1 was also upregulated with HDM exposure. In airway epithelial cells, HDM exposure significantly increased the mRNA expression of transcription factors OCT1, c-MYB and SRF. However, transcription factor HNF1A did not show any significant change with HDM exposure. Further, OCT1, c-MYB, and SRF were inhibited through their pharmacological inhibitors or siRNA knockdown. Notably, siRNA knockdown of OCT1 significantly reduced the expression of APP induced by HDM exposure, suggesting transcription factor OCT1 regulates HDM-induced APP expression in airway epithelial cells. Conclusion: Collectively, HDM induced APP expression in airway epithelial cells is regulated by transcriptional factor OCT1. Acknowledgments: Supported by NIH grant RF1 AG083029-01 (Combs and Venkatachalem) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.