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

Collynn F. Woeller; Thomas H. Thatcher; Juilee Thakar; Adam Cornwell; Matthew R. Smith; Dean P. Jones; Philip K. Hopke; Patricia J. Sime; Pamela Krahl; Timothy M. Mallon; Richard P. Phipps; Mark J. Utell

doi:10.1097/JOM.0000000000001691

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

Collynn F. Woeller^*, Thomas H. Thatcher, Juilee Thakar, Adam Cornwell, Matthew R. Smith, Dean P. Jones, Philip K. Hopke, Patricia J. Sime, Pamela Krahl, Timothy M. Mallon, Richard P. Phipps, Mark J. Utell

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Objective:Benzo(ghi)perylene (BghiP) and 1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin (HpCDD) were elevated in serum from personnel deployed to sites with open burn pits. Here, we investigated the ability of BghiP and HpCDD to regulate microRNA (miRNA) expression through the aryl hydrocarbon receptor (AHR).Methods:Human lung fibroblasts (HLFs) were exposed to BghiP and HpCDD. AHR activity was measured by reporter assay and gene expression. Deployment related miRNA were measured by quantitative polymerase chain reaction. AHR expression was depleted using siRNA.Results:BghiP displayed weak AHR agonist activity. HpCDD induced AHR activity in a dose-dependent manner. Let-7d-5p, miR-103-3p, miR-107, and miR-144-3p levels were significantly altered by HpCDD. AHR knockdown attenuated these effects.Conclusions:These studies reveal that miRNAs previously identified in sera from personnel deployed to sites with open burn pits are altered by HpCDD exposure in HLFs.

Original language	English
Pages (from-to)	S82-S89
Journal	Journal of Occupational and Environmental Medicine
Volume	61
DOIs	https://doi.org/10.1097/JOM.0000000000001691
State	Published - 1 Dec 2019
Externally published	Yes

Keywords

1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin
Benzo(ghi)perylene
biomarker
deployment
dioxin
exposure
human lung fibroblasts
microRNA
open burn pit

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Woeller, C. F., Thatcher, T. H., Thakar, J., Cornwell, A., Smith, M. R., Jones, D. P., Hopke, P. K., Sime, P. J., Krahl, P., Mallon, T. M., Phipps, R. P., & Utell, M. J. (2019). Exposure to Heptachlorodibenzo-p-dioxin (HpCDD) Regulates microRNA Expression in Human Lung Fibroblasts. Journal of Occupational and Environmental Medicine, 61, S82-S89. https://doi.org/10.1097/JOM.0000000000001691

@article{5b9fc367ff6b4c229493eb900c9df543,

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

abstract = "Objective:Benzo(ghi)perylene (BghiP) and 1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin (HpCDD) were elevated in serum from personnel deployed to sites with open burn pits. Here, we investigated the ability of BghiP and HpCDD to regulate microRNA (miRNA) expression through the aryl hydrocarbon receptor (AHR).Methods:Human lung fibroblasts (HLFs) were exposed to BghiP and HpCDD. AHR activity was measured by reporter assay and gene expression. Deployment related miRNA were measured by quantitative polymerase chain reaction. AHR expression was depleted using siRNA.Results:BghiP displayed weak AHR agonist activity. HpCDD induced AHR activity in a dose-dependent manner. Let-7d-5p, miR-103-3p, miR-107, and miR-144-3p levels were significantly altered by HpCDD. AHR knockdown attenuated these effects.Conclusions:These studies reveal that miRNAs previously identified in sera from personnel deployed to sites with open burn pits are altered by HpCDD exposure in HLFs.",

keywords = "1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin, Benzo(ghi)perylene, biomarker, deployment, dioxin, exposure, human lung fibroblasts, microRNA, open burn pit",

author = "Woeller, {Collynn F.} and Thatcher, {Thomas H.} and Juilee Thakar and Adam Cornwell and Smith, {Matthew R.} and Jones, {Dean P.} and Hopke, {Philip K.} and Sime, {Patricia J.} and Pamela Krahl and Mallon, {Timothy M.} and Phipps, {Richard P.} and Utell, {Mark J.}",

note = "Publisher Copyright: {\textcopyright} 2019 American College of Occupational and Environmental Medicine. Unauthorized reproduction of this article is prohibited.",

year = "2019",

month = dec,

day = "1",

doi = "10.1097/JOM.0000000000001691",

language = "English",

volume = "61",

pages = "S82--S89",

journal = "Journal of Occupational and Environmental Medicine",

issn = "1076-2752",

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Woeller, CF, Thatcher, TH, Thakar, J, Cornwell, A, Smith, MR, Jones, DP, Hopke, PK, Sime, PJ, Krahl, P, Mallon, TM, Phipps, RP & Utell, MJ 2019, 'Exposure to Heptachlorodibenzo-p-dioxin (HpCDD) Regulates microRNA Expression in Human Lung Fibroblasts', Journal of Occupational and Environmental Medicine, vol. 61, pp. S82-S89. https://doi.org/10.1097/JOM.0000000000001691

TY - JOUR

T1 - Exposure to Heptachlorodibenzo-p-dioxin (HpCDD) Regulates microRNA Expression in Human Lung Fibroblasts

AU - Woeller, Collynn F.

AU - Thatcher, Thomas H.

AU - Thakar, Juilee

AU - Cornwell, Adam

AU - Smith, Matthew R.

AU - Jones, Dean P.

AU - Hopke, Philip K.

AU - Sime, Patricia J.

AU - Krahl, Pamela

AU - Mallon, Timothy M.

AU - Phipps, Richard P.

AU - Utell, Mark J.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Objective:Benzo(ghi)perylene (BghiP) and 1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin (HpCDD) were elevated in serum from personnel deployed to sites with open burn pits. Here, we investigated the ability of BghiP and HpCDD to regulate microRNA (miRNA) expression through the aryl hydrocarbon receptor (AHR).Methods:Human lung fibroblasts (HLFs) were exposed to BghiP and HpCDD. AHR activity was measured by reporter assay and gene expression. Deployment related miRNA were measured by quantitative polymerase chain reaction. AHR expression was depleted using siRNA.Results:BghiP displayed weak AHR agonist activity. HpCDD induced AHR activity in a dose-dependent manner. Let-7d-5p, miR-103-3p, miR-107, and miR-144-3p levels were significantly altered by HpCDD. AHR knockdown attenuated these effects.Conclusions:These studies reveal that miRNAs previously identified in sera from personnel deployed to sites with open burn pits are altered by HpCDD exposure in HLFs.

AB - Objective:Benzo(ghi)perylene (BghiP) and 1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin (HpCDD) were elevated in serum from personnel deployed to sites with open burn pits. Here, we investigated the ability of BghiP and HpCDD to regulate microRNA (miRNA) expression through the aryl hydrocarbon receptor (AHR).Methods:Human lung fibroblasts (HLFs) were exposed to BghiP and HpCDD. AHR activity was measured by reporter assay and gene expression. Deployment related miRNA were measured by quantitative polymerase chain reaction. AHR expression was depleted using siRNA.Results:BghiP displayed weak AHR agonist activity. HpCDD induced AHR activity in a dose-dependent manner. Let-7d-5p, miR-103-3p, miR-107, and miR-144-3p levels were significantly altered by HpCDD. AHR knockdown attenuated these effects.Conclusions:These studies reveal that miRNAs previously identified in sera from personnel deployed to sites with open burn pits are altered by HpCDD exposure in HLFs.

KW - 1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin

KW - Benzo(ghi)perylene

KW - biomarker

KW - deployment

KW - dioxin

KW - exposure

KW - human lung fibroblasts

KW - microRNA

KW - open burn pit

UR - http://www.scopus.com/inward/record.url?scp=85076083062&partnerID=8YFLogxK

U2 - 10.1097/JOM.0000000000001691

DO - 10.1097/JOM.0000000000001691

M3 - Article

C2 - 31800454

AN - SCOPUS:85076083062

SN - 1076-2752

VL - 61

SP - S82-S89

JO - Journal of Occupational and Environmental Medicine

JF - Journal of Occupational and Environmental Medicine

ER -

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

Abstract

Keywords

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