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Therapeutic treatment of dietary docosahexaenoic acid for particle-induced pulmonary inflammation in Balb/c mice

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Abstract

Objective and design

The omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has been reported to suppress inflammation. Pulmonary inflammation can be directly linked to exposure of various occupational and man-made particles leading to pulmonary diseases. Therapeutic treatments are lacking for particle-induced pulmonary inflammation. These studies evaluated DHA as a therapeutic treatment for semi-acute and chronic particle-induced pulmonary inflammation.

Methods

Balb/c mice were oropharyngeal instilled with hydrophobic multi-walled carbon nanotube (MWCNT) or hydrophilic crystalline silica (SiO2) either as one instillation (semi-acute) or once a week for 4 weeks (chronic). One week later, the mice were placed on either a control or 1% DHA-containing diet for 3 weeks (semi-acute) or 12 weeks (chronic). Mice were assessed for inflammatory signaling within the lung lavage fluid, impact on phagolysosomal membrane permeability, shifts of macrophage phenotype gene expression (M1, M2a, M2b, and M2c), and pulmonary histopathology.

Results

DHA increased pulmonary inflammatory markers and lung pathology when mice were exposed to SiO2. There were trending decreases of inflammatory markers for MWCNT-exposed mice with DHA treatment, however, mostly not statistically significant.

Conclusion

The anti-inflammatory benefits of DHA treatment depend upon the type of inflammatory particle, magnitude of inflammation, and duration of treatment.

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Acknowledgements

The authors would like to thank the technical support from the CEHS Core Facilities: 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 384-well CFX Maestro’s; Lou Herritt, and Pamela Shaw within the CEHS Core facilities; UM’s Laboratory Animal Resources technicians and facility; and Iheanyi Amadi for help with lung airway thickness analysis.

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). The content within is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 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.

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Authors and Affiliations

  1. Department of Biomedical and Pharmaceutical Sciences, Center for Environmental Health Sciences, University of Montana, 32 Campus Drive, Missoula, MT, 59812, USA

    Paige Fletcher, Raymond F. Hamilton Jr., Joseph F. Rhoderick, Britten Postma, Mary Buford & Andrij Holian

  2. Department of Food Science and Human Nutrition, Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA

    James J. Pestka

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Contributions

PF designed and carried out the in vivo studies, analyzed the in vivo and ex vivo studies, and performed statistical analysis. PF wrote the first draft of the manuscript. RFH setup the ex vivo studies, assisted in lung pathology scoring, and provided statistical advice. JFR assisted with mRNA quantification by qPCR and provided qPCR advice. BP and MB assisted PF with the in vivo studies. JJP assisted PF with logistics of the in vivo studies and supplied the DHA microalgal oil within the diets. AH assisted PF with overall study design and coordination. All authors contributed to furthering the manuscript’s drafts and approved the final manuscript.

Corresponding author

Correspondence to Paige Fletcher.

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Conflict of interest

The authors have no conflicts of interest or competing interests to declare.

Ethical approval

The animal use protocol (035-16AHCEHS-062816) was approved by the University of Montana Institutional Animal Care and Use Committee for all mouse studies described within this manuscript. The mice are maintained in microisolation containers within the BSL-2 Laboratory Animal Resources facility at the University of Montana in the accordance with the Guide for the Care and Use of Laboratory Animals. The animal care facility at the University of Montana is staffed with full-time veterinarians that are AAALAC accredited. Mice were monitored on a daily basis along with during/after exposure to particles. Mice were anesthetized with isoflurane before particle or vehicle control instillations so as not to use any restraints or cause distress. All procedures within these studies caused minimal discomfort to the mice; however, in any cases where it was deemed that the mice were in pain or distress (adverse body weight, abnormal activity, poor grooming, abnormal posture) the animal was humanely euthanized.

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Fletcher, P., Hamilton, R.F., Rhoderick, J.F. et al. Therapeutic treatment of dietary docosahexaenoic acid for particle-induced pulmonary inflammation in Balb/c mice. Inflamm. Res. 70, 359–373 (2021). https://doi.org/10.1007/s00011-021-01443-4

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  • DOI: https://doi.org/10.1007/s00011-021-01443-4

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