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Lamellar leukocyte infiltration and involvement of IL-6 during oligofructose-induced equine laminitis development. - PubMed - NCBI
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Vet Immunol Immunopathol. 2011 Nov 15;144(1-2):120-8. doi: 10.1016/j.vetimm.2011.07.016. Epub 2011 Jul 26.

Lamellar leukocyte infiltration and involvement of IL-6 during oligofructose-induced equine laminitis development.

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1
The Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton 4343, Australia. michelle.visser@utoronto.ca

Abstract

Laminitis is known to involve deregulation of proteases and destruction of the lamellar basement membrane with the host inflammatory response also playing a role. Leukocyte infiltration has been well characterized in the black walnut model of laminitis induction, but not in carbohydrate induced models. Increased gene expression of multiple cytokines, including IL-6, has also been implicated in laminitis development. Using real time PCR, immunohistochemistry and zymography methods, we characterize leukocyte infiltration and IL-6 gene expression in oligofructose (OF) induced laminitis. As well, we use two in vitro models to investigate a role for IL-6 in protease regulation. Laminitis was induced in normal standardbred horses (n=5) by alimentary OF dosing and lamellar biopsies were obtained throughout the 48 h experimental period. Lamellar explants and keratinocytes were also isolated from clinically normal horses for in vitro experiments. We found infiltration of calprotectin-positive leukocytes (monocytes and neutrophils) at 18-24h post oligofructose dosing, while IL-6 gene expression was increased as early as 12h post dosing. Additionally, while we found that IL-6 did not cause significant BM damage in vitro, it did result in increased secreted proMMP-9 levels from lamellar explants. Thus, we find that leukocyte infiltration does occur during oligofructose-induced laminitis development, however, IL-6 gene expression in the lamellae may precede leukocyte infiltration. Additionally, we show IL-6 plays a role in increasing the level of proMMP-9 in vivo in a manner that does not involve keratinocytes.

PMID:
21831454
DOI:
10.1016/j.vetimm.2011.07.016
[Indexed for MEDLINE]
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