Anti-fibrotic Actions of Equine Interleukin-10 on Transforming Growth Factor-Beta1-Stimulated Dermal Fibroblasts Isolated From Limbs of Horses.
Authors: Wise Lyn M, Stuart Gabriella S, Sriutaisuk Kevalee, Adams Brooke R, Riley Christopher B, Theoret Christine L
Journal: Frontiers in veterinary science
Summary
Exuberant granulation tissue (proud flesh) in equine limb wounds results from dysregulated fibroblast activity driven by elevated transforming growth factor-beta1 (TGF-β1) and insufficient interleukin-10 (IL-10) signalling; this research examined whether supplementing equine IL-10 could counteract the fibrotic cascade at the cellular level. Researchers isolated dermal fibroblasts from six horses' limb skin, exposed them to recombinant equine IL-10 with and without equine TGF-β1, and measured myofibroblast differentiation, collagen deposition, cell contractility and fibrotic gene expression using immunofluorescence, gel contraction assays and qPCR. When TGF-β1 stimulated fibroblasts, cells became more contractile and dramatically upregulated alpha-smooth muscle actin, collagen types 1 and 3, and multiple matrix metalloproteinases (MMP-1, -2, -9); critically, equine IL-10 suppressed this response by limiting contractility, reducing type 3 collagen and alpha-smooth muscle actin production, downregulating the genes for type 3 collagen and MMP-9, and upregulating MMP-1—a collagen-degrading enzyme potentially beneficial for tissue remodelling. These findings demonstrate that IL-10 exerts direct anti-fibrotic effects on equine fibroblasts, likely through modulation of TGF-β1 receptor and IL-10 receptor expression, suggesting that IL-10 therapy warrants further investigation as a targeted treatment to limit pathological fibrosis in problem equine wounds.
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Practical Takeaways
- •IL-10 therapy may offer a future treatment option for excessive granulation tissue in equine limb wounds by limiting fibroblast proliferation and collagen deposition
- •Current findings are limited to cell culture; clinical efficacy and safety in living horses requires further investigation before therapeutic application
- •Understanding the molecular mechanisms of fibrosis regulation helps explain why some horses struggle with exuberant granulation tissue and may guide wound management strategies
Key Findings
- •Equine IL-10 significantly limited fibroblast contractility and alpha-smooth muscle actin expression induced by TGF-β1
- •IL-10 reduced type 3 collagen production and decreased mRNA levels of Col3a1 and MMP9 while increasing MMP1
- •IL-10 modulated receptor gene expression by increasing TGF-β receptor 3 and IL-10 receptor 1 expression following TGF-β1 stimulation
- •These findings suggest IL-10 has therapeutic potential to counteract the pro-fibrotic effects of TGF-β1 in exuberant granulation tissue