TY - JOUR
T1 - Genetic ablation of soluble TNF does not affect lesion size and functional recovery after moderate spinal cord injury in mice
AU - Ellman, Ditte Gry
AU - Degn, Matilda
AU - Lund, Minna Christiansen
AU - Clausen, Bettina Hjelm
AU - Novrup, Hans Gram
AU - Flæng, Simon Bertram
AU - Jørgensen, Louise Helskov
AU - Suntharalingam, Lujitha
AU - Svenningsen, Åsa Fex
AU - Brambilla, Roberta
AU - Lambertsen, Kate Lykke
N1 - Funding Information:
This work was supported by The Carlsberg Foundation (2007 01 0176), the International Foundation for Research in Paraplegia (P128), the Danish Association for Paraplegics (RYK), Simon FougnerHartmann's Familiefond (Kate Lykke Lambertsen), Overl?geradets Legatudvalg, Odense University Hospital, Fonden til L?gevidenskabens Fremme, Kong Christian X's Fond, Institute of Molecular Medicine, SDU, the Health Faculty, SDU (Ditte Gry Ellman), NIH NINDS Grants NS084303-01A1 and 1R01NS094522-01, and The Miami Project To Cure Paralysis (Roberta Brambilla).
PY - 2016
Y1 - 2016
N2 - Traumatic spinal cord injury (SCI) is followed by an instant increase in expression of the microglial-derived proinflammatory cytokine tumor necrosis factor (TNF) within the lesioned cord. TNF exists both as membrane-anchored TNF (mTNF) and as cleaved soluble TNF (solTNF). We previously demonstrated that epidural administration of a dominant-negative inhibitor of solTNF, XPro1595, to the contused spinal cord resulted in changes in Iba1 protein expression in microglia/macrophages, decreased lesion volume, and improved locomotor function. Here, we extend our studies using mice expressing mTNF, but no solTNF (m T N F Δ / Δ), to study the effect of genetic ablation of solTNF on SCI. We demonstrate that TNF levels were significantly decreased within the lesioned spinal cord 3 days after SCI in m T N F Δ / Δ mice compared to littermates. This decrease did, however, not translate into significant changes in other pro- and anti-inflammatory cytokines (IL-10, IL-1β, IL-6, IL-5, IL-2, CXCL1, CCL2, or CCL5), despite a tendency towards increased IL-10 and decreased IL-1β, TNFR1, and TNFR2 levels in m T N F Δ / Δ mice. In addition, microglial and leukocyte infiltration, activation state (Iba1, CD11b, CD11c, CD45, and MHCII), lesion size, and functional outcome after moderate SCI were comparable between genotypes. Collectively, our data demonstrate that genetic ablation of solTNF does not significantly modulate postlesion outcome after SCI.
AB - Traumatic spinal cord injury (SCI) is followed by an instant increase in expression of the microglial-derived proinflammatory cytokine tumor necrosis factor (TNF) within the lesioned cord. TNF exists both as membrane-anchored TNF (mTNF) and as cleaved soluble TNF (solTNF). We previously demonstrated that epidural administration of a dominant-negative inhibitor of solTNF, XPro1595, to the contused spinal cord resulted in changes in Iba1 protein expression in microglia/macrophages, decreased lesion volume, and improved locomotor function. Here, we extend our studies using mice expressing mTNF, but no solTNF (m T N F Δ / Δ), to study the effect of genetic ablation of solTNF on SCI. We demonstrate that TNF levels were significantly decreased within the lesioned spinal cord 3 days after SCI in m T N F Δ / Δ mice compared to littermates. This decrease did, however, not translate into significant changes in other pro- and anti-inflammatory cytokines (IL-10, IL-1β, IL-6, IL-5, IL-2, CXCL1, CCL2, or CCL5), despite a tendency towards increased IL-10 and decreased IL-1β, TNFR1, and TNFR2 levels in m T N F Δ / Δ mice. In addition, microglial and leukocyte infiltration, activation state (Iba1, CD11b, CD11c, CD45, and MHCII), lesion size, and functional outcome after moderate SCI were comparable between genotypes. Collectively, our data demonstrate that genetic ablation of solTNF does not significantly modulate postlesion outcome after SCI.
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U2 - 10.1155/2016/2684098
DO - 10.1155/2016/2684098
M3 - Article
C2 - 28070141
AN - SCOPUS:85009127101
VL - 2016
JO - Mediators of Inflammation
JF - Mediators of Inflammation
SN - 0962-9351
M1 - 2684098
ER -