Gestational exposure to sidestream (Secondhand) cigarette smoke promotes transgenerational epigenetic transmission of exacerbated allergic asthma and bronchopulmonary dysplasia

Shashi P. Singh, Hitendra S. Chand, Raymond J. Langley, Neerad Mishra, Ted Barrett, Karin Rudolph, Carmen Tellez, Piotr T. Filipczak, Steve Belinsky, Ali I. Saeed, Aryaz Sheybani, Vernat Exil, Hemant Agarwal, Venkataramana Sidhaye, Thomas Sussan, Shyam Biswal, Mohan Sopori

Research output: Contribution to journalArticle

Abstract

Embryonic development is highly sensitive to xenobiotic toxicity and in utero exposure to environmental toxins affects physiological responses of the progeny. In the United States, the prevalence of allergic asthma (AA) is inexplicably rising and in utero exposure to cigarette smoke increases the risk of AA and bronchopulmonary dysplasia (BPD) in children and animal models. We reported that gestational exposure to sidestream cigarette smoke (SS), or secondhand smoke, promoted nicotinic acetylcholine receptor-dependent exacerbation of AA and BPD in mice. Recently, perinatal nicotine injections in rats were reported to induce peroxisome proliferator-activated receptor g-dependent transgenerational transmission of asthma. Herein, we show that first generation and second generation progeny from gestationally SS-exposed mice exhibit exacerbated AA and BPD that is not dependent on the decrease in peroxisome proliferator-activated receptor g levels. Lungs from these mice show strong eosinophilic infiltration, excessive Th2 polarization, marked airway hyperresponsiveness, alveolar simplification, decreased lung compliance, and decreased lung angiogenesis. At the molecular level, these changes are associated with increased RUNX3 expression, alveolar cell apoptosis, and the antiangiogenic factor GAX, and decreased expression of HIF-1α and proangiogenic factors NF-kB and VEGFR2 in the 7-d first generation and second generation lungs. Moreover, the lungs from these mice exhibit lower levels of microRNA (miR)-130a and increased levels of miR-16 and miR-221. These miRs regulate HIF-1a-regulated apoptotic, angiogenic, and immune pathways. Thus the intergenerational effects of gestational SS involve epigenetic regulation of HIF-1α through specific miRs contributing to increased incidence of AA and BPD in the progenies.

Original languageEnglish (US)
Pages (from-to)3815-3822
Number of pages8
JournalJournal of Immunology
Volume198
Issue number10
DOIs
StatePublished - May 15 2017

Fingerprint

Bronchopulmonary Dysplasia
Tobacco Smoke Pollution
Epigenomics
Tobacco Products
Asthma
Smoke
MicroRNAs
Lung
Peroxisome Proliferator-Activated Receptors
Alveolar Epithelial Cells
Lung Compliance
NF-kappa B
Environmental Exposure
Nicotinic Receptors
Xenobiotics
Nicotine
Embryonic Development
Animal Models
Apoptosis
Injections

ASJC Scopus subject areas

  • Immunology

Cite this

Gestational exposure to sidestream (Secondhand) cigarette smoke promotes transgenerational epigenetic transmission of exacerbated allergic asthma and bronchopulmonary dysplasia. / Singh, Shashi P.; Chand, Hitendra S.; Langley, Raymond J.; Mishra, Neerad; Barrett, Ted; Rudolph, Karin; Tellez, Carmen; Filipczak, Piotr T.; Belinsky, Steve; Saeed, Ali I.; Sheybani, Aryaz; Exil, Vernat; Agarwal, Hemant; Sidhaye, Venkataramana; Sussan, Thomas; Biswal, Shyam; Sopori, Mohan.

In: Journal of Immunology, Vol. 198, No. 10, 15.05.2017, p. 3815-3822.

Research output: Contribution to journalArticle

Singh, SP, Chand, HS, Langley, RJ, Mishra, N, Barrett, T, Rudolph, K, Tellez, C, Filipczak, PT, Belinsky, S, Saeed, AI, Sheybani, A, Exil, V, Agarwal, H, Sidhaye, V, Sussan, T, Biswal, S & Sopori, M 2017, 'Gestational exposure to sidestream (Secondhand) cigarette smoke promotes transgenerational epigenetic transmission of exacerbated allergic asthma and bronchopulmonary dysplasia', Journal of Immunology, vol. 198, no. 10, pp. 3815-3822. https://doi.org/10.4049/jimmunol.1700014
Singh, Shashi P. ; Chand, Hitendra S. ; Langley, Raymond J. ; Mishra, Neerad ; Barrett, Ted ; Rudolph, Karin ; Tellez, Carmen ; Filipczak, Piotr T. ; Belinsky, Steve ; Saeed, Ali I. ; Sheybani, Aryaz ; Exil, Vernat ; Agarwal, Hemant ; Sidhaye, Venkataramana ; Sussan, Thomas ; Biswal, Shyam ; Sopori, Mohan. / Gestational exposure to sidestream (Secondhand) cigarette smoke promotes transgenerational epigenetic transmission of exacerbated allergic asthma and bronchopulmonary dysplasia. In: Journal of Immunology. 2017 ; Vol. 198, No. 10. pp. 3815-3822.
@article{29a528ec7ea14f32bca7aa22e6b77806,
title = "Gestational exposure to sidestream (Secondhand) cigarette smoke promotes transgenerational epigenetic transmission of exacerbated allergic asthma and bronchopulmonary dysplasia",
abstract = "Embryonic development is highly sensitive to xenobiotic toxicity and in utero exposure to environmental toxins affects physiological responses of the progeny. In the United States, the prevalence of allergic asthma (AA) is inexplicably rising and in utero exposure to cigarette smoke increases the risk of AA and bronchopulmonary dysplasia (BPD) in children and animal models. We reported that gestational exposure to sidestream cigarette smoke (SS), or secondhand smoke, promoted nicotinic acetylcholine receptor-dependent exacerbation of AA and BPD in mice. Recently, perinatal nicotine injections in rats were reported to induce peroxisome proliferator-activated receptor g-dependent transgenerational transmission of asthma. Herein, we show that first generation and second generation progeny from gestationally SS-exposed mice exhibit exacerbated AA and BPD that is not dependent on the decrease in peroxisome proliferator-activated receptor g levels. Lungs from these mice show strong eosinophilic infiltration, excessive Th2 polarization, marked airway hyperresponsiveness, alveolar simplification, decreased lung compliance, and decreased lung angiogenesis. At the molecular level, these changes are associated with increased RUNX3 expression, alveolar cell apoptosis, and the antiangiogenic factor GAX, and decreased expression of HIF-1α and proangiogenic factors NF-kB and VEGFR2 in the 7-d first generation and second generation lungs. Moreover, the lungs from these mice exhibit lower levels of microRNA (miR)-130a and increased levels of miR-16 and miR-221. These miRs regulate HIF-1a-regulated apoptotic, angiogenic, and immune pathways. Thus the intergenerational effects of gestational SS involve epigenetic regulation of HIF-1α through specific miRs contributing to increased incidence of AA and BPD in the progenies.",
author = "Singh, {Shashi P.} and Chand, {Hitendra S.} and Langley, {Raymond J.} and Neerad Mishra and Ted Barrett and Karin Rudolph and Carmen Tellez and Filipczak, {Piotr T.} and Steve Belinsky and Saeed, {Ali I.} and Aryaz Sheybani and Vernat Exil and Hemant Agarwal and Venkataramana Sidhaye and Thomas Sussan and Shyam Biswal and Mohan Sopori",
year = "2017",
month = "5",
day = "15",
doi = "10.4049/jimmunol.1700014",
language = "English (US)",
volume = "198",
pages = "3815--3822",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - Gestational exposure to sidestream (Secondhand) cigarette smoke promotes transgenerational epigenetic transmission of exacerbated allergic asthma and bronchopulmonary dysplasia

AU - Singh, Shashi P.

AU - Chand, Hitendra S.

AU - Langley, Raymond J.

AU - Mishra, Neerad

AU - Barrett, Ted

AU - Rudolph, Karin

AU - Tellez, Carmen

AU - Filipczak, Piotr T.

AU - Belinsky, Steve

AU - Saeed, Ali I.

AU - Sheybani, Aryaz

AU - Exil, Vernat

AU - Agarwal, Hemant

AU - Sidhaye, Venkataramana

AU - Sussan, Thomas

AU - Biswal, Shyam

AU - Sopori, Mohan

PY - 2017/5/15

Y1 - 2017/5/15

N2 - Embryonic development is highly sensitive to xenobiotic toxicity and in utero exposure to environmental toxins affects physiological responses of the progeny. In the United States, the prevalence of allergic asthma (AA) is inexplicably rising and in utero exposure to cigarette smoke increases the risk of AA and bronchopulmonary dysplasia (BPD) in children and animal models. We reported that gestational exposure to sidestream cigarette smoke (SS), or secondhand smoke, promoted nicotinic acetylcholine receptor-dependent exacerbation of AA and BPD in mice. Recently, perinatal nicotine injections in rats were reported to induce peroxisome proliferator-activated receptor g-dependent transgenerational transmission of asthma. Herein, we show that first generation and second generation progeny from gestationally SS-exposed mice exhibit exacerbated AA and BPD that is not dependent on the decrease in peroxisome proliferator-activated receptor g levels. Lungs from these mice show strong eosinophilic infiltration, excessive Th2 polarization, marked airway hyperresponsiveness, alveolar simplification, decreased lung compliance, and decreased lung angiogenesis. At the molecular level, these changes are associated with increased RUNX3 expression, alveolar cell apoptosis, and the antiangiogenic factor GAX, and decreased expression of HIF-1α and proangiogenic factors NF-kB and VEGFR2 in the 7-d first generation and second generation lungs. Moreover, the lungs from these mice exhibit lower levels of microRNA (miR)-130a and increased levels of miR-16 and miR-221. These miRs regulate HIF-1a-regulated apoptotic, angiogenic, and immune pathways. Thus the intergenerational effects of gestational SS involve epigenetic regulation of HIF-1α through specific miRs contributing to increased incidence of AA and BPD in the progenies.

AB - Embryonic development is highly sensitive to xenobiotic toxicity and in utero exposure to environmental toxins affects physiological responses of the progeny. In the United States, the prevalence of allergic asthma (AA) is inexplicably rising and in utero exposure to cigarette smoke increases the risk of AA and bronchopulmonary dysplasia (BPD) in children and animal models. We reported that gestational exposure to sidestream cigarette smoke (SS), or secondhand smoke, promoted nicotinic acetylcholine receptor-dependent exacerbation of AA and BPD in mice. Recently, perinatal nicotine injections in rats were reported to induce peroxisome proliferator-activated receptor g-dependent transgenerational transmission of asthma. Herein, we show that first generation and second generation progeny from gestationally SS-exposed mice exhibit exacerbated AA and BPD that is not dependent on the decrease in peroxisome proliferator-activated receptor g levels. Lungs from these mice show strong eosinophilic infiltration, excessive Th2 polarization, marked airway hyperresponsiveness, alveolar simplification, decreased lung compliance, and decreased lung angiogenesis. At the molecular level, these changes are associated with increased RUNX3 expression, alveolar cell apoptosis, and the antiangiogenic factor GAX, and decreased expression of HIF-1α and proangiogenic factors NF-kB and VEGFR2 in the 7-d first generation and second generation lungs. Moreover, the lungs from these mice exhibit lower levels of microRNA (miR)-130a and increased levels of miR-16 and miR-221. These miRs regulate HIF-1a-regulated apoptotic, angiogenic, and immune pathways. Thus the intergenerational effects of gestational SS involve epigenetic regulation of HIF-1α through specific miRs contributing to increased incidence of AA and BPD in the progenies.

UR - http://www.scopus.com/inward/record.url?scp=85019773412&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019773412&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1700014

DO - 10.4049/jimmunol.1700014

M3 - Article

C2 - 28381639

AN - SCOPUS:85019773412

VL - 198

SP - 3815

EP - 3822

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -