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Understanding the Link Between Inflammation and Muscle Satellite Cells in the Horse
As an athletic animal, the horse performs a variety of activities throughout its life. With improvements in care, the equine population is living longer and remaining active and competing at increasingly older ages. Both advancing age and exercise result in increased concentrations of circulating and local cytokines, including interleukin (IL)-1β, IL-6, IL-8, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. Athletic endeavors in the aged horse may further increase the pro-inflammatory environment in the muscle, decreasing the ability to react appropriately to exercise. Poor response to exercise limits the athletic ability of geriatric horses, thus reducing their useful life span and potentially increasing the risk of injury. Satellite cells are muscle stem cells that reside adjacent to muscle fibers in skeletal muscle and are at least partially responsible for both maintenance of muscle mass and muscle hypertrophy. Normally, these cells exist in a quiescent state, becoming active, proliferating and differentiating in response to specific stimuli. Growth factors and cytokines present during hypertrophy and following exercise affect satellite cell activity. While the specific effects of cytokines on satellite cells are not well established, cytokines can both positively and negatively influence satellite cell and myoblast proliferation and differentiation. Equine satellite cells are comparable to satellite cells isolated from other species, exhibiting a fibroblast-like morphology in culture after activation and expressing desmin, an intermediate filament protein specific to muscle cells. Further, they differentiate into multinucleated myotubes which express myosin heavy chain, a fundamental property of myogenic cells. Understanding the effect of cytokines on equine satellite cell function will allow us to determine the mechanisms responsible for the poor response to exercise. Preliminary data indicates that the pro-inflammatory cytokines IL-1β and IL-6 inhibit myogenesis. C2C12 myoblasts cultured with 1.0 ng/mL IL-1β exhibit impaired fusion compared with controls (P < 0.01). Further, C2C12 myoblasts cultured with 10 ng/mL IL-6 exhibit decreased proliferation and decreased fusion compared with controls (P < 0.01). Ongoing work is examining the effects of these cytokines on satellite cells from young and adult horses. The pro-inflammatory environment in aged horses may inhibit exercise induced satellite cell activity, thereby diminishing exercise induced hypertrophy. As more horses are surviving and competing into their 20’s, more research is required to understand the response of these animals to exercise during normal aging.
Keywords:
cytokines, horse, satellite cells