Central IL-4 promotes a neuroprotective and anti-inflammatory brain environment following peripheral LPS injection
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Series/Report no.:2012 Edward F. Hayes Graduate Research Forum. 26th
Aging is associated with the loss of appropriate immune regulation resulting in increased inflammatory status within the central nervous system (CNS). Microglia, the innate immune cell of the CNS, are particularly sensitive to age-associated dysregulation and promote an exaggerated inflammatory response following a peripheral or central immune challenge in aged animals. Recently our lab found that after a peripheral immune challenge, microglia from adult, but not aged, mice upregulated interleukin (IL)-4 receptor-alpha (IL-4Rα), the receptor for the anti-inflammatory cytokine IL-4. The functional consequence of impaired IL-4Rα upregulation was insensitivity to the anti-inflammatory promoting effects of IL-4. Thus, to further characterize potential consequences of impaired IL-4Rα upregulation on aged microglia, we conducted a series of studies investigating the extent to which a peripheral immune challenge with lipopolysaccharide (LPS) and central injection of IL-4 promoted IL-4Rα upregulation and the induction of anti-inflammatory and neuroprotective markers in vivo. We provide evidence that upregulation of IL-4Rα is necessary to promote a strong neurotrophin and arginase response following exposure to IL-4. Furthermore, we show that a functional consequence of exaggerated arginase expression in microglia is increased polyamine production resulting in high levels of CCL2 and increased recruitment of macrophages to the brain. This is important because IL-4 levels are typically elevated in the CNS following tissue damage. Thus, impaired IL-4Rα upregulation in aged mice may prevent an appropriate arginase and polyamine response necessary for tissue repair and growth following CNS injury.
Biological Sciences: 1st Place (The Ohio State University Edward F. Hayes Graduate Research Forum)
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