Dimethylarginine dimethylaminohydrolase (DDAH) overexpression enhances wound repair in airway epithelial cells exposed to agricultural organic dust

Deepak Chandra, Jill A Poole, Kristina L Bailey, Elizabeth Staab, Jenea M. Sweeter, Jane M. DeVasure, Debra Romberger, Todd A Wyatt

Research output: Contribution to journalArticle

Abstract

Objective: Workers exposed to dusts from concentrated animal feeding operations have a high prevalence of pulmonary diseases. These exposures lead to chronic inflammation and aberrant airway remodeling. Previous work shows that activating cAMP-dependent protein kinase (PKA) enhances airway epithelial wound repair while activating protein kinase C (PKC) inhibits wound repair. Hog barn dust extracts slow cell migration and wound repair via a PKC-dependent mechanism. Further, blocking nitric oxide (NO) production in bronchial epithelial cells prevents PKA activation. We hypothesized that blocking an endogenous NO inhibitor, asymmetric dimethylarginine, by overexpressing dimethylarginine dimethylaminohydrolase mitigates the effects of hog dust extract on airway epithelial would repair. Materials/methods: We cultured primary tracheal epithelial cells in monolayers from both wild-type (WT) and dimethylarginine dimethylaminohydrolase overexpressing C57Bl/6 (DDAH 1 transgenic) mice and measured wound repair using the electric cell impedance sensing system. Results: Wound closure in epithelial cells from WT mice occurred within 24 h in vitro. In contrast, treatment of the WT cell monolayers with 5% hog dust extract prevented significant NO-stimulated wound closure. In cells from DDAH 1 transgenic mice, control wounds were repaired up to 8 h earlier than seen in WT mice. A significant enhancement of wound repair was observed in DDAH cells compared to WT cells treated with hog dust extract for 24 h. Likewise, cells from DDAH 1 transgenic mice demonstrated increased NO and PKA activity and decreased hog dust extract-stimulated PKC. Discussion/conclusion: Preserving the NO signal through endogenous inhibition of asymmetric dimethylarginine enhances wound repair even in the presence of dust exposure.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalInhalation Toxicology
Volume30
Issue number3
DOIs
StatePublished - Feb 23 2018

Fingerprint

Dust
Repair
Epithelial Cells
Nitric Oxide
Wounds and Injuries
Protein Kinase C
Transgenic Mice
Protein Kinases
Monolayers
Electric batteries
EphA2 Receptor
Pulmonary diseases
Airway Remodeling
Cyclic AMP-Dependent Protein Kinases
dimethylargininase
Animals
Electric Impedance
Chemical activation
Lung Diseases
Cell Movement

Keywords

  • Epithelial wound repair
  • dimethylarginine dimethylaminohydrolase
  • nitric oxide
  • protein kinase C

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Dimethylarginine dimethylaminohydrolase (DDAH) overexpression enhances wound repair in airway epithelial cells exposed to agricultural organic dust. / Chandra, Deepak; Poole, Jill A; Bailey, Kristina L; Staab, Elizabeth; Sweeter, Jenea M.; DeVasure, Jane M.; Romberger, Debra; Wyatt, Todd A.

In: Inhalation Toxicology, Vol. 30, No. 3, 23.02.2018, p. 133-139.

Research output: Contribution to journalArticle

@article{5668b74cb9344852b604d805d691a623,
title = "Dimethylarginine dimethylaminohydrolase (DDAH) overexpression enhances wound repair in airway epithelial cells exposed to agricultural organic dust",
abstract = "Objective: Workers exposed to dusts from concentrated animal feeding operations have a high prevalence of pulmonary diseases. These exposures lead to chronic inflammation and aberrant airway remodeling. Previous work shows that activating cAMP-dependent protein kinase (PKA) enhances airway epithelial wound repair while activating protein kinase C (PKC) inhibits wound repair. Hog barn dust extracts slow cell migration and wound repair via a PKC-dependent mechanism. Further, blocking nitric oxide (NO) production in bronchial epithelial cells prevents PKA activation. We hypothesized that blocking an endogenous NO inhibitor, asymmetric dimethylarginine, by overexpressing dimethylarginine dimethylaminohydrolase mitigates the effects of hog dust extract on airway epithelial would repair. Materials/methods: We cultured primary tracheal epithelial cells in monolayers from both wild-type (WT) and dimethylarginine dimethylaminohydrolase overexpressing C57Bl/6 (DDAH 1 transgenic) mice and measured wound repair using the electric cell impedance sensing system. Results: Wound closure in epithelial cells from WT mice occurred within 24 h in vitro. In contrast, treatment of the WT cell monolayers with 5{\%} hog dust extract prevented significant NO-stimulated wound closure. In cells from DDAH 1 transgenic mice, control wounds were repaired up to 8 h earlier than seen in WT mice. A significant enhancement of wound repair was observed in DDAH cells compared to WT cells treated with hog dust extract for 24 h. Likewise, cells from DDAH 1 transgenic mice demonstrated increased NO and PKA activity and decreased hog dust extract-stimulated PKC. Discussion/conclusion: Preserving the NO signal through endogenous inhibition of asymmetric dimethylarginine enhances wound repair even in the presence of dust exposure.",
keywords = "Epithelial wound repair, dimethylarginine dimethylaminohydrolase, nitric oxide, protein kinase C",
author = "Deepak Chandra and Poole, {Jill A} and Bailey, {Kristina L} and Elizabeth Staab and Sweeter, {Jenea M.} and DeVasure, {Jane M.} and Debra Romberger and Wyatt, {Todd A}",
year = "2018",
month = "2",
day = "23",
doi = "10.1080/08958378.2018.1474976",
language = "English (US)",
volume = "30",
pages = "133--139",
journal = "Inhalation Toxicology",
issn = "0895-8378",
publisher = "Informa Healthcare",
number = "3",

}

TY - JOUR

T1 - Dimethylarginine dimethylaminohydrolase (DDAH) overexpression enhances wound repair in airway epithelial cells exposed to agricultural organic dust

AU - Chandra, Deepak

AU - Poole, Jill A

AU - Bailey, Kristina L

AU - Staab, Elizabeth

AU - Sweeter, Jenea M.

AU - DeVasure, Jane M.

AU - Romberger, Debra

AU - Wyatt, Todd A

PY - 2018/2/23

Y1 - 2018/2/23

N2 - Objective: Workers exposed to dusts from concentrated animal feeding operations have a high prevalence of pulmonary diseases. These exposures lead to chronic inflammation and aberrant airway remodeling. Previous work shows that activating cAMP-dependent protein kinase (PKA) enhances airway epithelial wound repair while activating protein kinase C (PKC) inhibits wound repair. Hog barn dust extracts slow cell migration and wound repair via a PKC-dependent mechanism. Further, blocking nitric oxide (NO) production in bronchial epithelial cells prevents PKA activation. We hypothesized that blocking an endogenous NO inhibitor, asymmetric dimethylarginine, by overexpressing dimethylarginine dimethylaminohydrolase mitigates the effects of hog dust extract on airway epithelial would repair. Materials/methods: We cultured primary tracheal epithelial cells in monolayers from both wild-type (WT) and dimethylarginine dimethylaminohydrolase overexpressing C57Bl/6 (DDAH 1 transgenic) mice and measured wound repair using the electric cell impedance sensing system. Results: Wound closure in epithelial cells from WT mice occurred within 24 h in vitro. In contrast, treatment of the WT cell monolayers with 5% hog dust extract prevented significant NO-stimulated wound closure. In cells from DDAH 1 transgenic mice, control wounds were repaired up to 8 h earlier than seen in WT mice. A significant enhancement of wound repair was observed in DDAH cells compared to WT cells treated with hog dust extract for 24 h. Likewise, cells from DDAH 1 transgenic mice demonstrated increased NO and PKA activity and decreased hog dust extract-stimulated PKC. Discussion/conclusion: Preserving the NO signal through endogenous inhibition of asymmetric dimethylarginine enhances wound repair even in the presence of dust exposure.

AB - Objective: Workers exposed to dusts from concentrated animal feeding operations have a high prevalence of pulmonary diseases. These exposures lead to chronic inflammation and aberrant airway remodeling. Previous work shows that activating cAMP-dependent protein kinase (PKA) enhances airway epithelial wound repair while activating protein kinase C (PKC) inhibits wound repair. Hog barn dust extracts slow cell migration and wound repair via a PKC-dependent mechanism. Further, blocking nitric oxide (NO) production in bronchial epithelial cells prevents PKA activation. We hypothesized that blocking an endogenous NO inhibitor, asymmetric dimethylarginine, by overexpressing dimethylarginine dimethylaminohydrolase mitigates the effects of hog dust extract on airway epithelial would repair. Materials/methods: We cultured primary tracheal epithelial cells in monolayers from both wild-type (WT) and dimethylarginine dimethylaminohydrolase overexpressing C57Bl/6 (DDAH 1 transgenic) mice and measured wound repair using the electric cell impedance sensing system. Results: Wound closure in epithelial cells from WT mice occurred within 24 h in vitro. In contrast, treatment of the WT cell monolayers with 5% hog dust extract prevented significant NO-stimulated wound closure. In cells from DDAH 1 transgenic mice, control wounds were repaired up to 8 h earlier than seen in WT mice. A significant enhancement of wound repair was observed in DDAH cells compared to WT cells treated with hog dust extract for 24 h. Likewise, cells from DDAH 1 transgenic mice demonstrated increased NO and PKA activity and decreased hog dust extract-stimulated PKC. Discussion/conclusion: Preserving the NO signal through endogenous inhibition of asymmetric dimethylarginine enhances wound repair even in the presence of dust exposure.

KW - Epithelial wound repair

KW - dimethylarginine dimethylaminohydrolase

KW - nitric oxide

KW - protein kinase C

UR - http://www.scopus.com/inward/record.url?scp=85047415185&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047415185&partnerID=8YFLogxK

U2 - 10.1080/08958378.2018.1474976

DO - 10.1080/08958378.2018.1474976

M3 - Article

C2 - 29793367

AN - SCOPUS:85047415185

VL - 30

SP - 133

EP - 139

JO - Inhalation Toxicology

JF - Inhalation Toxicology

SN - 0895-8378

IS - 3

ER -