In vivo and in vitro evidence of the involvement of CXCL1, a keratinocyte-derived chemokine, in equine laminitis.

The research investigates the role of the chemokine CXCL1 in equine laminitis, a painful condition in horses. It provides evidence from in vivo and in vitro studies, suggesting that CXCL1 could play an early role in the disease, and potential new treatments using chemokine receptor antagonists may be beneficial.

Study Objective and Methods

• The paper focuses on evaluating the regulation of C-X-C motif ligand 1 (CXCL1), an influential chemokine of epithelial origin, within the context of equine laminitis, both in vitro and in vivo.
• Twenty adult horses were involved in the study. The experiment used real-time quantitative polymerase chain reaction (PCR) to examine the expression of CXCL1 in different samples from the animals, including laminae, liver, skin, and lung.
• The researchers used the black walnut extract (BWE) model of laminitis and also conducted tests on cultured equine epithelial cells (EpCs).
• Tissues were obtained from control animals, and at different stages after BWE administration: at 1.5 hours (early time point [ETP]), at the onset of leukopenia (developmental time point [DTP]), and at the onset of lameness (LAM).
• The EpCs were exposed to various conditions, including Toll-like/Nod receptor ligands, oxidative stress agents, and reduced atmospheric oxygen (3%).
• In situ PCR was used to identify which laminar cell types were expressing CXCL1 mRNA.

Study Findings

• The research discovered significant increases in laminar CXCL1 mRNA concentrations in the ETP and DTP groups. Smaller increases were also observed in other tissues and organs in horses.
• In the cultured EpCs, increases in CXCL1 mRNA concentration were observed after exposing the cells to lipopolysaccharide (LPS), xanthine/xanthine oxidase, and H(2)O(2). Hypoxic conditions (reduced oxygen) further increased the LPS-induced rise in CXCL1 mRNA.
• It was determined that CXCL1 gene expression was localized to laminar EpCs, endothelial cells, and emigrating leukocytes.

Conclusions and Implications

• The results indicate that CXCL1 potentially plays an early, perhaps initiating, role in neutrophil accumulation in the BWE laminitis model, and that laminar keratinocytes are an important source of this chemokine.
• These findings can guide the development of new therapeutic strategies for equine laminitis, potentially harnessing chemokine receptor antagonists.