期刊
JOURNAL OF NEUROSCIENCE
卷 34, 期 49, 页码 16424-16432出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2927-14.2014
关键词
chrondroitinase ABC; inflammation; macrophage polarization; proteoglycans; spinal cord injury
资金
- Medical Research Council (Senior Non-Clinical Fellowship Award) [G1002055]
- Rosetrees Trust [JS16/M276]
- Medical Research Council [G1002055] Funding Source: researchfish
- Rosetrees Trust [M276] Funding Source: researchfish
- MRC [G1002055] Funding Source: UKRI
Chondroitinase ABC(ChABC) has striking effects on promoting neuronal plasticity after spinal cord injury (SCI), but little is known about its involvement in other pathological mechanisms. Recent work showed that ChABC might also modulate the immune response by promoting M2 macrophage polarization. Here we investigate in detail the immunoregulatory effects of ChABC after SCI in rats. Initially, we examined the expression profile of 16M1/M2 macrophage polarization markers at 3 h and 7 d postinjury. ChABC treatment had a clear effect on the immune signature after SCI. More specifically, ChABC increased the expression of the anti-inflammatory cytokine IL-10, accompanied by a reduction in the proinflammatory cytokine IL-12B in injured spinal tissue. These effects were associated with a distinct, IL-10-mediated anti-inflammatory response in ChABC-treated spinal cords. Mechanistically, we show that IL-10 expression is driven by tissue injury and macrophage infiltration, while the p38 MAPK is the central regulator of IL-10 expression in vivo. These findings provide novel insights into the effects of ChABC in the injured spinal cord and explain its immunoregulatory activity.
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