In vivo and in vitro evidence of the involvement of CXCL1, a keratinocyte-derived chemokine, in equine laminitis.
Authors: Faleiros R R, Leise B B, Westerman T, Yin C, Nuovo G J, Belknap J K
Journal: Journal of veterinary internal medicine
Summary
# Editorial Summary: CXCL1 and Equine Laminitis This 2009 study examined the chemokine CXCL1—a signalling molecule produced by epithelial cells—as a potential driver of the inflammatory cascade in laminitis, using both clinical disease models and laboratory cell cultures to understand its role. Researchers tracked CXCL1 expression across tissue samples from horses at different stages of black walnut extract–induced laminitis, whilst simultaneously exposing cultured equine epithelial cells to various inflammatory triggers (bacterial lipopolysaccharide, oxidative stressors, and low oxygen) to identify what stimulates its production. Laminar CXCL1 mRNA increased dramatically in the earliest phase of laminitis (163-fold increase) and remained substantially elevated during disease development (21-fold), with the chemokine being produced specifically by laminar epithelial cells, blood vessel endothelium, and infiltrating immune cells. The findings suggest CXCL1 functions as an early amplifier of the neutrophil-driven inflammatory response characteristic of acute laminitis, particularly under conditions combining bacterial endotoxaemia with tissue hypoxia—a pattern clinically relevant to both grain overload and systemic infection scenarios. These results point toward potential therapeutic targets beyond current anti-inflammatory approaches, specifically chemokine receptor antagonists that could interrupt neutrophil recruitment at the laminar level before irreversible tissue damage occurs.
Read the full abstract on PubMed
Practical Takeaways
- •CXCL1 appears to be an early trigger for neutrophil accumulation in laminitis pathogenesis; understanding this mechanism may lead to new therapeutic targets using chemokine receptor antagonists as adjunct treatments
- •Laminar keratinocytes are identified as a key source of CXCL1, making epithelial cell protection during acute laminitis crises a potential therapeutic focus
- •The rapid upregulation of CXCL1 within 1.5 hours of triggering (before lameness onset) suggests this chemokine could be a biomarker for early detection and intervention in laminitis cases
Key Findings
- •Laminar CXCL1 mRNA concentrations increased 163-fold at early time point (1.5 hours) and 21-fold at developmental time point in the black walnut extract laminitis model
- •Cultured equine epithelial cells showed significant CXCL1 upregulation after exposure to lipopolysaccharide (28-fold), xanthine/xanthine oxidase (3.5-fold), and hydrogen peroxide (2-fold)
- •Hypoxia enhanced LPS-induced CXCL1 mRNA expression (P=0.007)
- •CXCL1 gene expression was localized to laminar epithelial cells, endothelial cells, and emigrating leukocytes, suggesting keratinocytes are a primary source of this neutrophil-recruiting chemokine