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Respiratory research2025; 26(1); 126; doi: 10.1186/s12931-025-03194-w

MARCKS protein is a potential target in a naturally occurring equine model of neutrophilic asthma.

Abstract: Asthma is a chronic inflammatory airway disease that affects millions of people worldwide. Horses develop asthma spontaneously and serve as a relevant model for multiple phenotypes and endotypes of human asthma. In horses with equine asthma (EA), environmental organic dust triggers increased inflammatory cytokines, excess airway mucus, reversible bronchoconstriction, and airway inflammation. In horses with severe EA (sEA), lower airway inflammation is invariably neutrophilic, making sEA a potential model for severe neutrophilic asthma in humans. Alveolar macrophages (AM) and airway neutrophils contribute to lower airway inflammation and tissue damage through the release of cytokines and toxic mediators including reactive oxygen species. Previous work shows that the Myristoylated Alanine Rich C Kinase Substrate (MARCKS) protein is increased in activated macrophages and neutrophils and is an essential regulator of inflammatory functions in these cell types. We hypothesized that MARCKS protein would be increased in bronchoalveolar lavage (BAL) cells from horses with EA, and that in vitro inhibition of MARCKS with a specific inhibitor peptide known as MyristoylAted N-terminal Sequence (MANS), would diminish cytokine production and respiratory burst. Methods: BAL cells from two populations of healthy and asthmatic horses were evaluated for cytology and MARCKS protein analysis. Isolated alveolar macrophages and peripheral blood neutrophils were stimulated with zymosan to evaluate MARCKS inhibition in cytokine secretion and respiratory burst. Results: We found increased levels of normalized MARCKS protein in total BAL cells from horses with asthma compared to normal horses. MARCKS inhibition with the MANS peptide had no effect on zymosan-stimulated release of tumor necrosis factor alpha (TNFα) or interleukin-8 (IL-8) from alveolar macrophages but did attenuate zymosan-stimulated respiratory burst in both alveolar macrophages and peripheral blood neutrophils. Conclusions: These findings point to a possible role for MARCKS in the pathophysiology of neutrophilic equine asthma and support further investigation of MARCKS as a novel anti-inflammatory target for severe neutrophilic asthma.
© 2025. The Author(s).
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Publication Date: 2025-04-02 PubMed ID: 40176021PubMed Central: PMC11967018DOI: 10.1186/s12931-025-03194-wGoogle Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article investigates the role of a protein called MARCKS in equine asthma (EA), a form of asthma in horses, which might also shed light on human asthma. It was found that the MARCKS protein was higher in horses with EA and it could be a potential target for therapeutic treatment.

Background

  • Equine asthma (EA) is a disease in horses, which parallels multiple phenotypes of human asthma.
  • The study is rooted in the hypothesis that Myristoylated Alanine Rich C Kinase Substrate (MARKS) protein, which is critical in regulating inflammation in alveolar macrophages and neutrophils (two types of defense cells in mammals), might be playing an essential role in EA.
  • Environmental organic dust is reported to intensify the symptoms in horses with severe EA (sEA) like excess mucus in the airway, bronchoconstriction, and airway inflammation.

Methods

  • Bronchoalveolar lavage (BAL) cells from healthy horses and horses with asthma were collected and evaluated for cytology and MARCKS protein levels.
  • A specific inhibitor peptide known as Myristoylated N-terminal Sequence (MANS), designed to suppress MARCKS, was used on alveolar macrophages and peripheral blood neutrophils to observe its effect on cytokine secretion and respiratory burst.

Results

  • The researchers found out that horses with asthma had notably higher levels of MARCKS protein than healthy horses.
  • Meanwhile, the MANS peptide was deemed ineffective in influencing the release of TNFα or IL-8 from alveolar macrophages.
  • However, it was successful in mitigating the zymosan-stimulated respiratory burst in both alveolar macrophages and peripheral blood neutrophils.

Conclusions

  • Based on the findings, the researchers suggested that MARCKS could be potentially influential in the pathophysiology of equine asthma, and can be a focus for further research on severe neutrophilic asthma.
  • As a novel anti-inflammatory target, MARCKS holds potential in the development of new treatment modalities for asthma.

Cite This Article

APA
Conley HE, Davis KU, Adler KB, Lavoie JP, Sheats MK. (2025). MARCKS protein is a potential target in a naturally occurring equine model of neutrophilic asthma. Respir Res, 26(1), 126. https://doi.org/10.1186/s12931-025-03194-w

Publication

Respiratory research
ISSN: 1465-993X
NlmUniqueID: 101090633
Country: England
Language: English
Volume: 26
Issue: 1
Pages: 126
PII: 126

Researcher Affiliations

Conley, Haleigh E
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.
  • Comparative Medicine Institute, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.
Davis, Kaori Uchiumi
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.
  • Comparative Medicine Institute, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.
Adler, Kenneth B
  • Comparative Medicine Institute, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.
  • Department of Molecular and Biomedical Science, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.
Lavoie, Jean-Pierre
  • Département des Sciences Cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, QC, J2S 2M2, Canada.
Sheats, M Katie
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA. mkpeed@ncsu.edu.
  • Comparative Medicine Institute, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA. mkpeed@ncsu.edu.

MeSH Terms

  • Animals
  • Asthma / metabolism
  • Asthma / veterinary
  • Asthma / drug therapy
  • Asthma / immunology
  • Asthma / pathology
  • Horses
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Neutrophils / immunology
  • Neutrophils / pathology
  • Myristoylated Alanine-Rich C Kinase Substrate
  • Disease Models, Animal
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / metabolism
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Horse Diseases / metabolism
  • Horse Diseases / drug therapy
  • Horse Diseases / immunology
  • Macrophages, Alveolar / metabolism
  • Macrophages, Alveolar / drug effects
  • Cytokines / metabolism
  • Cells, Cultured

Grant Funding

  • T32 OD011130 / NIH HHS
  • D17EQ-029 / Morris Animal Foundation

Conflict of Interest Statement

Declarations. Ethics approval and consent to participate: Procedures and protocols for population A were approved by the North Carolina State University Institutional Animal Care and Use Committee (IACUC 16-0740O and 19–779). Samples for Population B were obtained from the Equine Respiratory Tissue Bank (ERTB) (Lavoie laboratory). Consent for publication: Not applicable. Competing interests: HC - The author declares that they have no competing interests. KD - The author declares that they have no competing interests. KA - Patents planned, issued or pending: Biomarck Corporation, Durham, NC. METHODS FOR REGULATING INFLAMMATORY MEDIATORS AND PEPTIDES USEFUL THEREIN. Inventors: Kenneth Adler, Suji Takashi, Indu Parikh, Linda Martin, and Yuehuva Li.Assignment: BioMarck and NC State University. Filed: 6/4/2009 US Patent: 8,563,689; Granted: October 22, 2013. KD - The author declares that they have no competing interests. MKS - The author declares that they have no competing interests.

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