Details:

Alternative Title:
Inhal Toxicol
Publisher's site:
http://dx.doi.org/10.1080/08958378.2018.1474976
Personal Author:
Chandra, Deepak ; Poole, Jill A. ; Bailey, Kristina L. ; Staab, Elizabeth ; Sweeter, Jenea M. ; ... More +
Chandra, Deepak ; Poole, Jill A. ; Bailey, Kristina L. ; Staab, Elizabeth ; Sweeter, Jenea M. ; DeVasure, Jane M. ; Romberger, Debra J. ; Wyatt, Todd A. Less -
Description:
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 (DDAH1 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 hr in vitro. In contrast, treatment of the WT cell monolayers with 5% hog dust extract prevented significant NO-stimulated wound closure. In cells from DDAH1 transgenic mice, control wounds were repaired up to 8 hours 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 hr. Likewise, cells from DDAH1 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.


Subject:
[+]
Amidohydrolases
Animal Husbandry
Animals
Arginine
Article
Cells, Cultured
Cyclic AMP-Dependent Protein Kinases
Dimethylarginine Dimethylaminohydrolase
Dust
Epithelial Cells
Epithelial Wound Repair
Mice, Inbred C57BL
Mice, Transgenic
Nitric Oxide
Protein Kinase C
Trachea
Wound Healing
Nitric Oxide
Protein Kinase C

Source:
Inhal Toxicol. 30(3):133-139
Pubmed ID:
29793367
Pubmed Central ID:
PMC6176920
Document Type:
Journal Article
Funding:
IK6 BX003781/BX/BLRD VA/United States ; R01 AA017993/AA/NIAAA NIH HHS/United States ; U54OH010162/ACL HHS/United States ; R01 OH008539/OH/NIOSH CDC HHS/United States ; R01 AG053553/AG/NIA NIH HHS/United States ; ... More +
IK6 BX003781/BX/BLRD VA/United States ; R01 AA017993/AA/NIAAA NIH HHS/United States ; U54OH010162/ACL HHS/United States ; R01 OH008539/OH/NIOSH CDC HHS/United States ; R01 AG053553/AG/NIA NIH HHS/United States ; R01 ES019325/ES/NIEHS NIH HHS/United States ; I01 BX003635/BX/BLRD VA/United States ; U54 OH010162/OH/NIOSH CDC HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:d371454ae9d5c357595336e79df395e59709af7f9f700d8bb3c6c8260d34cfa4
File Type:

Supporting Files

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