PMID- 29097425
OWN - NLM
STAT- MEDLINE
DCOM- 20190109
LR  - 20200930
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 314
IP  - 3
DP  - 2018 Mar 1
TI  - Docosahexaenoic acid enhances amphiregulin-mediated bronchial epithelial cell 
      repair processes following organic dust exposure.
PG  - L421-L431
LID - 10.1152/ajplung.00273.2017 [doi]
AB  - Injurious dust exposures in the agricultural workplace involve the release of 
      inflammatory mediators and activation of epidermal growth factor receptor (EGFR) 
      in the respiratory epithelium. Amphiregulin (AREG), an EGFR ligand, mediates 
      tissue repair and wound healing in the lung epithelium. Omega-3 fatty acids such 
      as docosahexaenoic acid (DHA) are also known modulators of repair and resolution 
      of inflammatory injury. This study investigated how AREG, DHA, and EGFR modulate 
      lung repair processes following dust-induced injury. Primary human bronchial 
      epithelial (BEC) and BEAS-2B cells were treated with an aqueous extract of swine 
      confinement facility dust (DE) in the presence of DHA and AREG or EGFR 
      inhibitors. Mice were exposed to DE intranasally with or without EGFR inhibition 
      and DHA. Using a decellularized lung scaffolding tissue repair model, BEC 
      recolonization of human lung scaffolds was analyzed in the context of DE, DHA, 
      and AREG treatments. Through these investigations, we identified an important 
      role for AREG in mediating BEC repair processes. DE-induced AREG release from 
      BEC, and DHA treatment following DE exposure, enhanced this release. Both DHA and 
      AREG also enhanced BEC repair capacities and rescued DE-induced recellularization 
      deficits. In vivo, DHA treatment enhanced AREG production following DE exposure, 
      whereas EGFR inhibitor-treated mice exhibited reduced AREG in their lung 
      homogenates. These data indicate a role for AREG in the process of tissue repair 
      after inflammatory lung injury caused by environmental dust exposure and 
      implicate a role for DHA in regulating AREG-mediated repair signaling in BEC.
FAU - Nordgren, Tara M
AU  - Nordgren TM
AD  - Pulmonary, Critical Care, Sleep and Allergy Division, Department of Internal 
      Medicine, University of Nebraska Medical Center , Omaha, Nebraska.
AD  - Division of Biomedical Sciences, School of Medicine, University of California 
      Riverside , Riverside, California.
FAU - Heires, Art J
AU  - Heires AJ
AD  - Pulmonary, Critical Care, Sleep and Allergy Division, Department of Internal 
      Medicine, University of Nebraska Medical Center , Omaha, Nebraska.
FAU - Bailey, Kristina L
AU  - Bailey KL
AD  - Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska.
AD  - Pulmonary, Critical Care, Sleep and Allergy Division, Department of Internal 
      Medicine, University of Nebraska Medical Center , Omaha, Nebraska.
FAU - Katafiasz, Dawn M
AU  - Katafiasz DM
AD  - Pulmonary, Critical Care, Sleep and Allergy Division, Department of Internal 
      Medicine, University of Nebraska Medical Center , Omaha, Nebraska.
FAU - Toews, Myron L
AU  - Toews ML
AD  - Department of Pharmacology and Experimental Neuroscience, University of Nebraska 
      Medical Center , Omaha, Nebraska.
FAU - Wichman, Christopher S
AU  - Wichman CS
AD  - Department of Biostatistics, University of Nebraska Medical Center , Omaha, 
      Nebraska.
FAU - Romberger, Debra J
AU  - Romberger DJ
AD  - Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska.
AD  - Pulmonary, Critical Care, Sleep and Allergy Division, Department of Internal 
      Medicine, University of Nebraska Medical Center , Omaha, Nebraska.
LA  - eng
GR  - R00 ES025819/ES/NIEHS NIH HHS/United States
GR  - K99 ES025819/ES/NIEHS NIH HHS/United States
GR  - R01 OH008539/OH/NIOSH CDC HHS/United States
GR  - R01 AG053553/AG/NIA NIH HHS/United States
GR  - U54 OH010162/OH/NIOSH CDC HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20171102
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Dust)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Amphiregulin/*metabolism
MH  - Animals
MH  - Bronchi/*cytology/drug effects/metabolism
MH  - Docosahexaenoic Acids/*pharmacology
MH  - Dust/*analysis
MH  - Environmental Exposure/*adverse effects
MH  - Epithelial Cells/*cytology/drug effects/metabolism
MH  - ErbB Receptors/metabolism
MH  - Humans
MH  - Lung Injury/etiology/metabolism/pathology/*prevention & control
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Signal Transduction
MH  - Swine
PMC - PMC5900355
OTO - NOTNLM
OT  - amphiregulin
OT  - bronchial epithelial cells
OT  - inflammation
OT  - organic dust
OT  - repair
EDAT- 2017/11/04 06:00
MHDA- 2019/01/10 06:00
PMCR- 2019/03/01
CRDT- 2017/11/04 06:00
PHST- 2017/11/04 06:00 [pubmed]
PHST- 2019/01/10 06:00 [medline]
PHST- 2017/11/04 06:00 [entrez]
PHST- 2019/03/01 00:00 [pmc-release]
AID - ajplung.00273.2017 [pii]
AID - L-00273-2017 [pii]
AID - 10.1152/ajplung.00273.2017 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2018 Mar 1;314(3):L421-L431. doi: 
      10.1152/ajplung.00273.2017. Epub 2017 Nov 2.