Regulation of IL-10 by chondroitinase ABC promotes a distinct immune response following spinal cord injury

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81 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)16424-16432
Number of pages9
JournalJournal of Neuroscience
Volume34
Issue number49
DOIs
Publication statusPublished - 3 Dec 2014

Keywords

  • Chrondroitinase ABC
  • Inflammation
  • Macrophage polarization
  • Proteoglycans
  • Spinal cord injury

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