TY - JOUR
T1 - Regulation of IL-10 by chondroitinase ABC promotes a distinct immune response following spinal cord injury
AU - Didangelos, Athanasios
AU - Iberl, Michaela
AU - Vinsland, Elin
AU - Bartus, Katalin
AU - Bradbury, Elizabeth
PY - 2014/12/3
Y1 - 2014/12/3
N2 - ChondroitinaseABC(ChABC) has striking effects on promoting neuronal plasticity after spinal cord injury (SCI), but little isknownabout 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/M2macrophage polarization markers at 3 h and 7 d postinjury.ChABCtreatment 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.
AB - ChondroitinaseABC(ChABC) has striking effects on promoting neuronal plasticity after spinal cord injury (SCI), but little isknownabout 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/M2macrophage polarization markers at 3 h and 7 d postinjury.ChABCtreatment 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.
KW - Chrondroitinase ABC
KW - Inflammation
KW - Macrophage polarization
KW - Proteoglycans
KW - Spinal cord injury
UR - http://www.scopus.com/inward/record.url?scp=84914670481&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2927-14.2014
DO - 10.1523/JNEUROSCI.2927-14.2014
M3 - Article
AN - SCOPUS:84914670481
SN - 0270-6474
VL - 34
SP - 16424
EP - 16432
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 49
ER -