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Stimulation of the Hepatic Toll‐like Receptor Signaling Pathway after Induction of Equine Laminitis Using Gastrointestinal Models
Author(s) -
Stokes Ashley Michelle,
McGeachy Matthew,
Carlisle Katherine,
Keowen Michael L,
Garza Frank
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1000.4
Subject(s) - laminitis , tlr2 , tlr4 , cd14 , downregulation and upregulation , toll like receptor , medicine , stimulation , signal transduction , innate immune system , immunology , receptor , inflammation , biology , microbiology and biotechnology , horse , paleontology , biochemistry , gene
The toll‐like receptor (TLR) signaling pathway is important in orchestrating innate immunity in response to many factors including circulating bacterial components. In cases of GI disruption, portal blood flow may lead to strong stimulation of the hepatic TLR signaling pathway with the subsequent systemic release of inflammatory mediators known to play a role in laminitis. Our objectives were to evaluate key mediators of the TLR signaling pathway in hepatic tissues after the use of two GI models of laminitis induction (black walnut extract (BWE) or carbohydrate overload (CHO) models). We examined TLR4, cluster of differentiation 14 (CD‐14), TLR2, phosphatidylinositol‐3‐kinase regulatory subunit 1 (PIK3R1), inhibitor of NF‐êB (INFKB), cyclooxygenase 2 (COX2), and interleukin 8 (IL‐8). Liver tissues (normal, BWE‐induced, CHO‐induced, and naturally‐acquired) were used in TaqMan RT‐PCR. CD14, TLR2, PIK3R1 and INFKB were significantly (p<0.05) upregulated in all laminitic horses. TLR4 was significantly upregulated in both models of laminitis induction, especially those following CHO which closely mimics the clinical presentation of a high percentage of laminitis cases. These findings demonstrate that TLR mediators are upregulated in cases of laminitis following GI disruption and systemic therapeutic intervention for laminitis prevention in these cases is warranted.