A High Docosahexaenoic Acid Diet Alters the Lung Inflammatory Response to Acute Dust Exposure

Abstract

Agricultural workers are at risk for the development of acute and chronic lung diseases due to their exposure to organic agricultural dusts. A diet intervention using the omega-3 fatty acid docosahexaenoic acid (DHA) has been shown to be an effective therapeutic approach for alleviating a dust-induced inflammatory response. We thus hypothesized a high-DHA diet would alter the dust-induced inflammatory response through the increased production of specialized pro-resolving mediators (SPMs). Mice were pre-treated with a DHA-rich diet 4 weeks before being intranasally challenged with a single dose of an extract made from dust collected from a concentrated swine feeding operation (HDE). This omega-3-fatty-acid-rich diet led to reduced arachidonic acid levels in the blood, enhanced macrophage recruitment, and increased the production of the DHA-derived SPM Resolvin D1 (RvD1) in the lung following HDE exposure. An assessment of transcript-level changes in the immune response demonstrated significant differences in immune pathway activation and alterations of numerous macrophage-associated genes among HDE-challenged mice fed a high DHA diet. Our data indicate that consuming a DHA-rich diet leads to the enhanced production of SPMs during an acute inflammatory challenge to dust, supporting a role for dietary DHA supplementation as a potential therapeutic strategy for reducing dust-induced lung inflammation.

A high docosahexaenoic acid diet alters lung inflammation and recovery following repetitive exposure to aqueous organic dust extracts

“…Male 6-8-week-old C57Bl/6 mice were purchased from Jackson Laboratories. After a 1-week acclimation period, mice were placed on a high DHA diet or a control diet lacking DHA, prepared as we have previously described [ 19 , 24 ]. Both the high DHA and standard modified diet were prepared by ENVIGO (Madison, WI, USA).…”

“…Both the high DHA and standard modified diet were prepared by ENVIGO (Madison, WI, USA). Both diets have been utilized in a previous study where we showed the effectiveness of the high DHA diet in altering the lung inflammatory response to a single exposure to HDE [ 24 ]. Briefly, in our study the AIN-93G diet was modified to replace soybean oil with high oleic safflower oil.…”

“…Moreover, omega-3 fatty acid supplementation between 6 g/day (EPA, 3.7 g + DHA, 2.5 g) versus 3 g/day (EPA, 1.8 g + DHA, 1.5 g) reduces exercise-induced bronchoconstriction and airway inflammation markers [ 29 ]. We have shown that airway inflammation induced after a single exposure to agricultural dust is largely inhibited by the high dose DHA supplementation for 4-weeks [ 24 ]. Mice had ad libitum access to food and water and were housed 5 mice/microisolator cage with cages changed every two weeks.…”

“…Whole blood was collected from the inferior vena cava and stored at −80°C until fatty acid analysis by gas chromatography (GC). Cryopreserved whole blood samples were thawed on ice, and 25 microliters were added into a 2 mL glass vial for direct transesterification using 250 microliters of 14% boron-trifluoride methanol and 250 microliters of hexane solution at 100°C for 60 minutes as previously reported [ 24 , 32 ]. A quantitative internal standard,17:0 heptadecanoic acid and a quantitative external standard, 15:0) were included.…”

Resolvin D1, therapeutic target in acute respiratory distress syndrome

“…The evaluation of RvD1 in the management of a range of disorders including neurodegenerative diseases ( Krashia et al, 2019 ; Miyazawa et al, 2020 ), fibrotic/electrical remodeling ( Hiram et al, 2020 ), diabetes mellitus and its complications ( Bathina and Das, 2021 ; Bathina et al, 2020 ; Bu et al, 2019 ; Yorek, 2018 ), acute kidney injury ( Luan et al, 2020 ), colitis-associated cancers ( Zhong et al, 2018 ), rheumatoid arthritis ( Özgül Özdemir et al, 2020 ), Sjogren's syndrome ( Yellepeddi et al, 2021 ), ocular allergic responses ( Dartt et al, 2019 ), and polycystic ovary syndrom (PCOS) ( Regidor et al, 2020 ) has shown promising results. In addition, lung diseases that have shown improvement following RvD1 administration include smoking-related asthma and COPD ( Bhat et al, 2020 , 2021 ), acute immune response and fibrotic lesions due to exposure to dust and nanomaterial ( Dominguez et al, 2020 ; Lim et al, 2020 ), lung adenocarcinoma ( Vannitamby et al, 2021 ), and airway inflammation in cystic fibrosis ( Ringholz et al, 2018 ), as well as ARDS. Here, we review the current knowledge on the effectiveness of RvD1 along with its mechanism of action and signaling routes in ALI/ARDS.…”