PMID- 35095496
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220510
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Sex-Specific Differences in Resolution of Airway Inflammation in Fat-1 Transgenic 
      Mice Following Repetitive Agricultural Dust Exposure.
PG  - 785193
LID - 10.3389/fphar.2021.785193 [doi]
LID - 785193
AB  - In agriculture industries, workers are at increased risk for developing pulmonary 
      diseases due to inhalation of agricultural dusts, particularly when working in 
      enclosed confinement facilities. Agricultural dusts inhalation leads to 
      unresolved airway inflammation that precedes the development and progression of 
      lung disease. We have previously shown beneficial effects of the omega-3 
      polyunsaturated fatty acid (omega-3 PUFA) DHA in protecting against the negative 
      inflammatory effects of repetitive dust exposure in the lung. Dietary 
      manipulation of pulmonary disease risk is an attractive and timely approach given 
      the contribution of an increased omega-6 to omega-3 PUFA ratio to low grade inflammation 
      and chronic disease in the Western diet. To prevent any confounding factors that 
      comes with dietary supplementation of omega-3 PUFA (different sources, purity, dose, 
      and duration), we employed a Fat-1 transgenic mouse model that convert omega-6 PUFA 
      to omega-3 PUFA, leading to a tissue omega-6 to omega-3 PUFA ratio of approximately 1:1. 
      Building on our initial findings, we hypothesized that attaining elevated tissue 
      levels of omega-3 PUFA would attenuate agricultural dust-induced lung inflammation 
      and its resolution. To test this hypothesis, we compared wild-type (WT) and Fat-1 
      transgenic mice in their response to aqueous extracts of agricultural dust (DE). 
      We also used a soluble epoxide hydrolase inhibitor (sEH) to potentiate the 
      effects of omega-3 PUFA, since sEH inhibitors have been shown to stabilize the 
      anti-inflammatory P450 metabolites derived from both omega-3 and omega-6 PUFA and promote 
      generation of specialized pro-resolving lipid mediators from omega-3 PUFA. Over a 
      three-week period, mice were exposed to a total of 15 intranasal instillations of 
      DE obtained from swine confinement buildings in the Midwest. We observed genotype 
      and sex-specific differences between the WT vs. Fat-1 transgenic mice in response 
      to repetitive dust exposure, where three-way ANOVA revealed significant main 
      effects of treatment, genotype, and sex. Also, Fat-1 transgenic mice displayed 
      reduced lymphoid aggregates in the lung following DE exposure as compared to WT 
      animals exposed to DE, suggesting improved resilience to the DE-induced 
      inflammatory effects. Overall, our data implicate a protective role of omega-3 FA in 
      the lung following repetitive dust exposure.
CI  - Copyright (c) 2022 Ulu, Velazquez, Burr, Sveiven, Yang, Bravo, Hammock and 
      Nordgren.
FAU - Ulu, Arzu
AU  - Ulu A
AD  - Division of Biomedical Sciences, School of Medicine, University of California, 
      Riverside, Riverside, CA, United States.
FAU - Velazquez, Jalene V
AU  - Velazquez JV
AD  - Division of Biomedical Sciences, School of Medicine, University of California, 
      Riverside, Riverside, CA, United States.
FAU - Burr, Abigail
AU  - Burr A
AD  - Division of Biomedical Sciences, School of Medicine, University of California, 
      Riverside, Riverside, CA, United States.
FAU - Sveiven, Stefanie N
AU  - Sveiven SN
AD  - Division of Biomedical Sciences, School of Medicine, University of California, 
      Riverside, Riverside, CA, United States.
FAU - Yang, Jun
AU  - Yang J
AD  - Department of Entomology and Nematology, University of California Davis 
      Comprehensive Cancer Center, University of California, Davis, Davis, CA, United 
      States.
FAU - Bravo, Carissa
AU  - Bravo C
AD  - Division of Biomedical Sciences, School of Medicine, University of California, 
      Riverside, Riverside, CA, United States.
FAU - Hammock, Bruce D
AU  - Hammock BD
AD  - Department of Entomology and Nematology, University of California Davis 
      Comprehensive Cancer Center, University of California, Davis, Davis, CA, United 
      States.
FAU - Nordgren, Tara M
AU  - Nordgren TM
AD  - Division of Biomedical Sciences, School of Medicine, University of California, 
      Riverside, Riverside, CA, United States.
AD  - Department of Environmental and Radiological Health Sciences, Colorado State 
      University, Fort Collins, CO, United States.
LA  - eng
GR  - P42 ES004699/ES/NIEHS NIH HHS/United States
GR  - R00 ES025819/ES/NIEHS NIH HHS/United States
GR  - R01 HL158926/HL/NHLBI NIH HHS/United States
GR  - R35 ES030443/ES/NIEHS NIH HHS/United States
PT  - Journal Article
DEP - 20220113
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8793679
OTO - NOTNLM
OT  - agricultural dust
OT  - fat-1 transgenic mice
OT  - omega-3 fatty acids
OT  - resolution of inflammation
OT  - sex
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/02/01 06:00
MHDA- 2022/02/01 06:01
PMCR- 2022/01/13
CRDT- 2022/01/31 05:55
PHST- 2021/09/28 00:00 [received]
PHST- 2021/12/23 00:00 [accepted]
PHST- 2022/01/31 05:55 [entrez]
PHST- 2022/02/01 06:00 [pubmed]
PHST- 2022/02/01 06:01 [medline]
PHST- 2022/01/13 00:00 [pmc-release]
AID - 785193 [pii]
AID - 10.3389/fphar.2021.785193 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Jan 13;12:785193. doi: 10.3389/fphar.2021.785193. 
      eCollection 2021.