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Session: Nutritional Immunology and Inflammation (Oral 23)

(OR23-03-24) Nutritional Modulation of Pulmonary Inflammation: The Role of DHA in Lipid Raft Dynamics and Respiratory Health

Monday, July 1, 2024
10:24 AM – 10:36 AM CT
Location:  W375A

    Presenting Author(s)

  • Rafia Virk, MS, PhD Candidate (she/her/hers)

    Graduate Research Assistant
    The University of North Carolina at Chapel Hill
    Morrisville, North Carolina, United States

    Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

    • Co-Author(s)

  • Kymberly Gowdy, PhD (she/her/hers)

    Associate Professor, Division of Pulmonary, Critical Care and Sleep Medicine
    Ohio State University
    Columbus, Ohio, United States

  • EP

    Edward R. Pennington

    The University of North Carolina at Chapel Hill, United States

  • Raz Shaikh, PhD

    Professor and Chair, Department of Nutrition
    Gillings School of Public Health, University of North Carolina at Chapel Hill

Objectives: This study investigated how docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid known for its anti-inflammatory properties, mitigates aspects of pulmonary inflammation. Focusing on alveolar macrophages (AMs), which are critical for maintaining respiratory homeostasis, we aimed to better understand mechanisms by which DHA reduces inflammation through reorganization of plasma membrane lipid rafts. We also confirmed DHA's anti-inflammatory role on specific markers of pulmonary inflammation in a mouse model of influenza.

Methods: We employed fluorescence-based methods to investigate effects of DHA on plasma membrane organization in MH-S cells, an AM cell-line, treated with either DHA or vehicle control. To further understand DHA’s role on lipid rafts at a molecular level, we created biomimetic membrane monolayers using Langmuir technology accompanied by coarse grain molecular dynamic (MD) simulations. Downstream inflammatory signaling in MH-S cells was evaluated using qRT-PCR, mass spectrometry, and ELISAs. Additionally, we harvested lung tissue from DHA-fed influenza-infected mice to measure select inflammatory markers.

Results: DHA increased the size of lipid rafts and decreased molecular packing of the MH-S plasma membrane. Incorporating DHA-containing phospholipids into biomimetic membranes led to condensing of membrane, which was reversed after cholesterol removal. MD simulations demonstrated that DHA enlarged lipid rafts by attracting cholesterol and sphingomyelin into rafts. DHA reduced the levels of specific inflammatory transcripts, oxylipins, and IL-6 secretion in activated MH-S cells. In influenza-infected mice, DHA increased anti-inflammatory oxylipins and decreased inflammatory gene expression.

Conclusions: Our findings support a model wherein DHA's integration into non-raft domains leads to the redistribution of sphingomyelin and cholesterol into lipid rafts, potentially controlling signaling pathways and thus reducing inflammation. These findings underscore the potential of DHA supplementation as a novel therapeutic strategy for pulmonary diseases characterized by inflammation, which warrants further clinical investigation.

Funding Sources: This work was supported by funding from the NIH (KGM, SRS).