Exposure to Heptachlorodibenzo-p-dioxin (HpCDD) Regulates microRNA Expression in Human Lung Fibroblasts

• Type of Material: Article
• Authors: Collynn F. Woeller, University of Rochester; Thomas H. Thatcher, University of Rochester; Juilee Thakar, University of Rochester; Adam Cornwell, University of Rochester; Matthew Smith, Emory University; Dean Jones, Emory University; Philip K. Hopke, University of Rochester; Patricia J. Sime, University of Rochester; Pamela Krahl, Uniformed Services University of the Health Sciences; Timothy M. Mallon, Uniformed Services University of the Health Sciences; Richard P. Phipps, University of Rochester; Mark J. Utell, University of Rochester
• Language: English
• Date: 2019-12-01
• Publisher: Lippincott Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 by the American College of Occupational and Environmental Medicine
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1097/JOM.0000000000001691
• Title of Journal or Parent Work: Journal of Occupational and Environmental Medicine
• Volume: 61
• Issue: 12
• Start Page: S82
• End Page: S89
• Grant/Funding Information: This work was supported by The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. grant number HT9404–13–1–0030, and the National Institute of Environmental Health Sciences Grant # P30-ES01247.
• Keywords: microRNA; 1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin; deployment; exposure; Life Sciences & Biomedicine; Adipogenesis; Deployment; open burn pit; Tryptophan; Science & Technology; Public, Environmental & Occupational Health; dioxin; biomarker; Receptor; Gene; Benzo(ghi)perylene; Polycyclic aromatic hydrocarbons; Homeostasis; Activation; human lung fibroblasts
• Research Categories: Biology, Biostatistics; Health Sciences, Occupational Health and Safety; Engineering, Biomedical; Health Sciences, Public Health

Abstract

Objective: Previous work demonstrated that deployment to sites with open burn pits altered serum microRNA (miRNA) levels. Here, we determined if identified deployment-related exposures alter miRNA expression in primary human lung fibroblasts (HLFs). Methods: Benzo(ghi)perylene (BghiP) and 1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin (HpCDD) were tested for their ability to activate the aryl hydrocarbon receptor (AHR) and induce changes in miRNA. AHR knockdown determined if changes were AHR-dependent. Results: HpCDD induced AHR activity in a dose-dependent manner. Four miRNAs linked to occupational open burn pit exposure were altered by HpCDD in HLFs. Knockdown of AHR attenuated changes in miRNA levels. Conclusions: These studies confirm that specific miRNAs, previously identified as different in sera from personnel deployed to sites with open burn pits, are altered by HpCDD exposure in human lung cells. HpCDD alters miRNA levels in an AHR dependent manner.