Potential role of the toll‐like receptor signaling pathway in equine laminitis

Abstract

Equine laminitis, a very common and painful disease of the laminar tissues of the foot, often results from conditions such as GI disruption (colic) or metabolic disease (Cushing's disease). Identification of the link between these primary diseases and the subsequent failure of the tissues of the foot is lacking and discovery would allow targeted development of therapeutics.Our objectives were to design equine primers/probes to evaluate key mediators of the Toll‐Like Receptor (TLR) Signaling Pathway to determine its role in laminitis. Specifically we examined TLR4, cluster of differentiation 14 (CD‐14), TLR2, phosphatidylinositol‐3‐kinase regulatory subunit 1 (PIK3R1), inhibitor of NF‐¿B (INFKB) and cyclooxygenase 2 (COX2).Primers and probes were designed from cloned equine samples, predicted sequences, and multi‐species compilations and were validated. Equine liver samples (normal n=6, laminitic n=15, clinical signs of metabolic disease n=4) were used in TaqMan RT‐PCR.Laminitic horses consistently upregulated these genes and metabolic cases (highly correlated with laminitis development) demonstrated significant (p<0.05) upregulation of CD14, TLR2, PIK3R1 and INFKB. These findings demonstrate key mediators of the TLR signaling pathway deserve further evaluation to determine their role in the pathogenesis of laminitis.Funding provided by the LSU Equine Health Studies Program.