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Frontiers in veterinary science2022; 9; 900453; doi: 10.3389/fvets.2022.900453

Withaferin A Inhibits Neutrophil Adhesion, Migration, and Respiratory Burst and Promotes Timely Neutrophil Apoptosis.

Abstract: Neutrophils play a major role in many equine conditions, including equine asthma, laminitis, and intestinal ischemia and reperfusion injury, and therefore represent an attractive target for innovative therapeutic approaches. Novel strategies for reducing neutrophilic inflammation include modulation of neutrophil functions and lifespan. Withaferin A (WFA) is a phytochemical with well-established and anti-inflammatory properties, but its direct effects on neutrophils are largely unknown. We hypothesized that WFA would inhibit adhesion, migration, and respiratory burst by equine neutrophils and promote timely apoptosis of primed equine neutrophils. Consistent with this hypothesis, our data show that WFA causes a significant, concentration-dependent inhibition of equine neutrophil adhesion, migration, and respiratory burst in response to diverse stimuli. Further, WFA treatment increased apoptosis of equine neutrophils exposed to GM-CSF for 24 h. This pro-apoptotic effect of WFA was not observed in unprimed neutrophils, nor at the 2-h time point relevant to our functional neutrophil experiments. Our data demonstrate that WFA may reduce neutrophil-mediated inflammation through multiple mechanisms, including suppression of inflammatory responses and promotion of apoptosis. Additional research is needed to elucidate the molecular mechanisms for these effects and evaluate the potential clinical use of WFA in veterinary and human patients.
Copyright © 2022 Bayless, Sheats and Jones.
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Publication Date: 2022-06-17 PubMed ID: 35782542PubMed Central: PMC9247543DOI: 10.3389/fvets.2022.900453Google 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 discusses how Withaferin A (WFA), a plant-based chemical, can obstruct certain functions of neutrophils, a type of white blood cell, in horses and encourage their timely death, consequently reducing inflammation. The study shows the potential for using WFA in treating conditions in horses like asthma and laminitis, that involve dysfunction of neutrophils.

Introduction: Neutrophils and their Role

  • Neutrophils, a type of white blood cell, play a crucial role in numerous health issues in horses, including asthma, laminitis, and intestinal ischemia and reperfusion injury.
  • The paper presents the argument that neutrophils are potentially significant targets for developing new methods for therapeutic intervention.

Objective of the Research

  • The objective of the study was to explore the effects of Withaferin A (WFA), a naturally occurring chemical, on horse neutrophils.
  • The researchers hypothesized that WFA would hinder several neutrophil activities such as adhesion, migration, and respiratory burst – all of these contribute to inflammation in the body.
  • Another presumed effect of WFA was to promote the timely death – also known as apoptosis – of activated neutrophils, thereby controlling the inflammation process.

Results of the Experiment

  • The outcomes of the study were in line with the initial hypothesis.
  • WFA demonstrated a significant and concentration-dependent inhibition of various functions of horse neutrophils – adhesion, migration, and respiratory burst.
  • Further, when neutrophils were exposed to Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) for 24 hours, WFA treatment resulted in an increase in apoptosis. So, WFA could accelerate the death of activated neutrophils, thus bringing the inflammation process under control.

Limitations and Scope of the Study

  • However, WFA didn’t induce apoptosis in neutrophils that were not activated and this pro-apoptotic effect was not observed at the 2-hour time point, which was relevant to this study.
  • The results suggest that WFA could potentially help reduce inflammation caused by neutrophils by both suppressing inflammatory responses and promoting controlled, timely apoptosis.
  • These findings open up avenues for further research to fully understand the molecular mechanisms involved and to evaluate the potential clinical use of WFA in veterinary and medical practice.

Cite This Article

APA
Bayless RL, Sheats MK, Jones SL. (2022). Withaferin A Inhibits Neutrophil Adhesion, Migration, and Respiratory Burst and Promotes Timely Neutrophil Apoptosis. Front Vet Sci, 9, 900453. https://doi.org/10.3389/fvets.2022.900453

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 9
Pages: 900453
PII: 900453

Researcher Affiliations

Bayless, Rosemary L
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.
Sheats, M Katie
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.
Jones, Samuel L
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.

Grant Funding

  • T32 OD011130 / NIH HHS

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Citations

This article has been cited 2 times.
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