title: Regulation of IL-10 by chondroitinase ABC promotes a distinct immune response following spinal cord injury.
abstract: 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 16 M1/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.
authors.affiliation: Wolfson Centre for Age Related Diseases, Guy's Campus, King's College London, London SE1 1UL, United Kingdom elizabeth.bradbury@kcl.ac.uk athanasios.didangelos@kcl.ac.uk.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Didangelos
authors.affiliation: Wolfson Centre for Age Related Diseases, Guy's Campus, King's College London, London SE1 1UL, United Kingdom.
authors.forename: Michaela
authors.initials: M
authors.lastname: Iberl
authors.affiliation: Wolfson Centre for Age Related Diseases, Guy's Campus, King's College London, London SE1 1UL, United Kingdom.
authors.forename: Elin
authors.initials: E
authors.lastname: Vinsland
authors.affiliation: Wolfson Centre for Age Related Diseases, Guy's Campus, King's College London, London SE1 1UL, United Kingdom.
authors.forename: Katalin
authors.initials: K
authors.lastname: Bartus
authors.affiliation: Wolfson Centre for Age Related Diseases, Guy's Campus, King's College London, London SE1 1UL, United Kingdom elizabeth.bradbury@kcl.ac.uk athanasios.didangelos@kcl.ac.uk.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Bradbury
mesh_terms: D000818:Animals; D019765:Chondroitin ABC Lyase / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D005786:Gene Expression Regulation; D007093:Imidazoles / Q000494:pharmacology; D056747:Immunomodulation / Q000187:drug effects* / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism*; D007278:Injections, Spinal; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000502:physiology; D008297:Male; D011509:Proteoglycans / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D007093:Imidazoles; D018836:Inflammation Mediators; D011509:Proteoglycans; D011725:Pyridines; D016753:Interleukin-10; D018664:Interleukin-12; D048051:p38 Mitogen-Activated Protein Kinases; D019765:Chondroitin ABC Lyase; C093642:SB 203580
keywords: chrondroitinase ABC; inflammation; macrophage polarization; proteoglycans; spinal cord injury