Dietary Docosahexaenoic Acid as a Potential Treatment for Semi-acute and Chronic Particle-Induced Pulmonary Inflammation in Balb/c Mice

Paige Fletcher; Raymond F. Hamilton; Joseph F. Rhoderick; Britten Postma; Mary Buford; James J. Pestka; Andrij Holian

doi:10.1007/s10753-021-01576-y

Dietary Docosahexaenoic Acid as a Potential Treatment for Semi-acute and Chronic Particle-Induced Pulmonary Inflammation in Balb/c Mice

Paige Fletcher
, Raymond F. Hamilton
, Joseph F. Rhoderick
, Britten Postma
, Mary Buford
, James J. Pestka
, Andrij Holian

Biomedical and Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Acute and chronic inflammation are vital contributing factors to pulmonary diseases which can be triggered by exposure to occupational and man-made particles; however, there are no established treatments. One potential treatment shown to have anti-inflammatory capabilities is the dietary supplement docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid found in fish oil. DHA’s anti-inflammatory mechanisms are unclear for particle-induced inflammation; therefore, this study evaluated DHA as a prophylactic treatment for semi-acute and chronic particle-induced inflammation in vivo. Balb/c mice were fed a control or 1% DHA diet and exposed to dispersion media, an inflammatory multi-walled carbon nanotube (MWCNT), or crystalline silica (SiO₂) either once (semi-acute) or once a week for 4 weeks (chronic). The hypothesis was that DHA will decrease pulmonary inflammatory markers in response to particle-induced inflammation. Results indicated that DHA had a trending anti-inflammatory effect in mice exposed to MWCNT. There was a general decrease in inflammatory signals within the lung lavage fluid and upregulation of M2c macrophage gene expression in the spleen tissue. In contrast, mice exposed to SiO₂ while on the DHA diet significantly increased most inflammatory markers. However, DHA stabilized the phagolysosomal membrane upon prolonged treatment. This indicated that DHA treatment may depend upon certain inflammatory particle exposures as well as the length of the exposure.

Original language	English
Pages (from-to)	677-694
Number of pages	18
Journal	Inflammation
Volume	45
Issue number	2
DOIs	https://doi.org/10.1007/s10753-021-01576-y
State	Published - Apr 2022

Funding

Paige Fletcher was supported by the Ruth L. Kirschstein NRSA Pre-doctoral Fellowship from the National Institute of Environmental Health Sciences (F31 ES028100). This research was supported by grants from the National Institute of Environmental Health Sciences (R01 ES023209 and R01 ES027353) and National Institute of General Medical Sciences (P30 GM103338). Paige Fletcher was awarded one of QIAGEN’s featured young scientists of the month (November 2018) where she received QIAGEN products that contributed to this research. The authors would like to thank the technical support from the Center for Environmental Health Sciences’ (CEHS) Core Facilities at University of Montana (UM): Inhalation and Pulmonary Physiology Core, Molecular Histology and Fluorescence Imaging Core, and the Fluorescence Cytometry Core. A special thank you to Dr. Joanna Kreitinger at Dermaxon and Dr. Sarjubhai Patel at FYR Diagnostics for use of their Bio-Rad 384-well CFX Maestro’s; Lou Herritt and Pamela Shaw within the CEHS Core facilities; Dr. Jack Harkema at Michigan State University for help with the semi-acute histopathology scoring; Iheanyi Amadi for help with lung airway wall thickness analysis; and UM’s Laboratory Animal Resources technicians and facility. The authors would like to thank the technical support from the Center for Environmental Health Sciences’ (CEHS) Core Facilities at University of Montana (UM): Inhalation and Pulmonary Physiology Core, Molecular Histology and Fluorescence Imaging Core, and the Fluorescence Cytometry Core. A special thank you to Dr. Joanna Kreitinger at Dermaxon and Dr. Sarjubhai Patel at FYR Diagnostics for use of their Bio-Rad 384-well CFX Maestro’s; Lou Herritt and Pamela Shaw within the CEHS Core facilities; Dr. Jack Harkema at Michigan State University for help with the semi-acute histopathology scoring; Iheanyi Amadi for help with lung airway wall thickness analysis; and UM’s Laboratory Animal Resources technicians and facility.

Funder number
P30 GM103338
R01 ES023209, R01 ES027353, F31 ES028100

Keywords

alveolar macrophage
crystalline silica
macrophage phenotype
multi-walled carbon nanotube
phagolysosomal membrane damage
pulmonary inflammation

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title = "Dietary Docosahexaenoic Acid as a Potential Treatment for Semi-acute and Chronic Particle-Induced Pulmonary Inflammation in Balb/c Mice",

abstract = "Acute and chronic inflammation are vital contributing factors to pulmonary diseases which can be triggered by exposure to occupational and man-made particles; however, there are no established treatments. One potential treatment shown to have anti-inflammatory capabilities is the dietary supplement docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid found in fish oil. DHA{\textquoteright}s anti-inflammatory mechanisms are unclear for particle-induced inflammation; therefore, this study evaluated DHA as a prophylactic treatment for semi-acute and chronic particle-induced inflammation in vivo. Balb/c mice were fed a control or 1\% DHA diet and exposed to dispersion media, an inflammatory multi-walled carbon nanotube (MWCNT), or crystalline silica (SiO2) either once (semi-acute) or once a week for 4 weeks (chronic). The hypothesis was that DHA will decrease pulmonary inflammatory markers in response to particle-induced inflammation. Results indicated that DHA had a trending anti-inflammatory effect in mice exposed to MWCNT. There was a general decrease in inflammatory signals within the lung lavage fluid and upregulation of M2c macrophage gene expression in the spleen tissue. In contrast, mice exposed to SiO2 while on the DHA diet significantly increased most inflammatory markers. However, DHA stabilized the phagolysosomal membrane upon prolonged treatment. This indicated that DHA treatment may depend upon certain inflammatory particle exposures as well as the length of the exposure.",

keywords = "alveolar macrophage, crystalline silica, macrophage phenotype, multi-walled carbon nanotube, phagolysosomal membrane damage, pulmonary inflammation",

author = "Paige Fletcher and Hamilton, \{Raymond F.\} and Rhoderick, \{Joseph F.\} and Britten Postma and Mary Buford and Pestka, \{James J.\} and Andrij Holian",

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AU - Postma, Britten

AU - Buford, Mary

AU - Pestka, James J.

AU - Holian, Andrij

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KW - crystalline silica

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Dietary Docosahexaenoic Acid as a Potential Treatment for Semi-acute and Chronic Particle-Induced Pulmonary Inflammation in Balb/c Mice

Abstract

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Keywords

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