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Orf virus interleukin‐10 and vascular endothelial growth factor‐E modulate gene expression in cultured equine dermal fibroblasts
Author(s) -
Wise Lyn M.,
Bodaan Christa J.,
Mercer Andrew A.,
Riley Christopher B.,
Theoret Christine L.
Publication year - 2016
Publication title -
veterinary dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.744
H-Index - 60
eISSN - 1365-3164
pISSN - 0959-4493
DOI - 10.1111/vde.12370
Subject(s) - vimentin , vascular endothelial growth factor , angiogenesis , wound healing , biology , inflammation , fibrosis , microbiology and biotechnology , tumor necrosis factor alpha , fibroblast , gene expression , pathology , immunology , cell culture , medicine , cancer research , gene , vegf receptors , immunohistochemistry , biochemistry , genetics
Background Wounds in horses often exhibit sustained inflammation and inefficient vascularization, leading to excessive fibrosis and clinical complications such as “proud flesh”. Orf virus‐derived proteins, vascular endothelial growth factor ( VEGF )‐E and interleukin (ov IL )‐10, enhance angiogenesis and control inflammation and fibrosis in skin wounds of laboratory animals. Hypothesis/Objectives The study aimed to determine if equine dermal cells respond to VEGF ‐E and ov IL ‐10. Equine dermal cells are expected to express VEGF and IL ‐10 receptors, so viral protein treatment is likely to alter cellular gene expression and behaviour in a manner conducive to healing. Animals Skin samples were harvested from the lateral thoracic wall of two healthy thoroughbred horses. Methods Equine dermal cells were isolated using a skin explant method and their phenotype assessed by immunofluorescence. Cells were treated with recombinant proteins, with or without inflammatory stimuli. Gene expression was examined using standard and quantitative reverse transcriptase PCR. Cell behaviour was evaluated in a scratch assay. Results Cultured cells were half vimentin +ve fibroblasts and half alpha smooth muscle actin +ve and vimentin +ve myofibroblasts. VEGF ‐E increased basal expression of IL ‐10 mRNA , whereas VEGF ‐A and collagenase‐1 mRNA expression was increased by ov IL ‐10. In cells exposed to inflammatory stimulus, both treatments dampened tumour necrosis factor mRNA expression, and ov IL ‐10 exacerbated expression of monocyte chemoattractant protein. Neither viral protein influenced cell migration greatly. Conclusions and clinical importance This study shows that VEGF ‐E and ov IL ‐10 are active on equine dermal cells and exert anti‐inflammatory and anti‐fibrotic effects that may enhance skin wound healing in horses.