Genetic Ablation of Soluble TNF Does Not Affect Lesion Size and Functional Recovery after Moderate Spinal Cord Injury in Mice
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...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/2684098 |
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| author | Ditte Gry Ellman Matilda Degn Minna Christiansen Lund Bettina Hjelm Clausen Hans Gram Novrup Simon Bertram Flæng Louise Helskov Jørgensen Lujitha Suntharalingam Åsa Fex Svenningsen Roberta Brambilla Kate Lykke Lambertsen |
| author_facet | Ditte Gry Ellman Matilda Degn Minna Christiansen Lund Bettina Hjelm Clausen Hans Gram Novrup Simon Bertram Flæng Louise Helskov Jørgensen Lujitha Suntharalingam Åsa Fex Svenningsen Roberta Brambilla Kate Lykke Lambertsen |
| author_sort | Ditte Gry Ellman |
| collection | DOAJ |
| description | 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 (mTNFΔ/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 mTNFΔ/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 mTNFΔ/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. |
| format | Article |
| id | doaj-art-1cc8ee5996ce486f869f8aa2caec05f7 |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1cc8ee5996ce486f869f8aa2caec05f72025-08-20T02:01:43ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/26840982684098Genetic Ablation of Soluble TNF Does Not Affect Lesion Size and Functional Recovery after Moderate Spinal Cord Injury in MiceDitte Gry Ellman0Matilda Degn1Minna Christiansen Lund2Bettina Hjelm Clausen3Hans Gram Novrup4Simon Bertram Flæng5Louise Helskov Jørgensen6Lujitha Suntharalingam7Åsa Fex Svenningsen8Roberta Brambilla9Kate Lykke Lambertsen10Neurobiology Research, Institute of Molecular Medicine, J.B. Winsloewsvej 21, st, 5000 Odense C, DenmarkDepartment of Diagnostics, Molecular Sleep Lab, Rigshospitalet, Nordre Ringvej 69, 2600 Glostrup, DenmarkNeurobiology Research, Institute of Molecular Medicine, J.B. Winsloewsvej 21, st, 5000 Odense C, DenmarkNeurobiology Research, Institute of Molecular Medicine, J.B. Winsloewsvej 21, st, 5000 Odense C, DenmarkNeurobiology Research, Institute of Molecular Medicine, J.B. Winsloewsvej 21, st, 5000 Odense C, DenmarkNeurobiology Research, Institute of Molecular Medicine, J.B. Winsloewsvej 21, st, 5000 Odense C, DenmarkDepartment of Pathology, Department of Clinical Research, SDU Muscle Research Cluster, University of Southern Denmark, J.B. Winsloewsvej 15, 5000 Odense C, DenmarkNeurobiology Research, Institute of Molecular Medicine, J.B. Winsloewsvej 21, st, 5000 Odense C, DenmarkNeurobiology Research, Institute of Molecular Medicine, J.B. Winsloewsvej 21, st, 5000 Odense C, DenmarkThe Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USANeurobiology Research, Institute of Molecular Medicine, J.B. Winsloewsvej 21, st, 5000 Odense C, DenmarkTraumatic 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 (mTNFΔ/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 mTNFΔ/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 mTNFΔ/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.http://dx.doi.org/10.1155/2016/2684098 |
| spellingShingle | Ditte Gry Ellman Matilda Degn Minna Christiansen Lund Bettina Hjelm Clausen Hans Gram Novrup Simon Bertram Flæng Louise Helskov Jørgensen Lujitha Suntharalingam Åsa Fex Svenningsen Roberta Brambilla Kate Lykke Lambertsen Genetic Ablation of Soluble TNF Does Not Affect Lesion Size and Functional Recovery after Moderate Spinal Cord Injury in Mice Mediators of Inflammation |
| title | Genetic Ablation of Soluble TNF Does Not Affect Lesion Size and Functional Recovery after Moderate Spinal Cord Injury in Mice |
| title_full | Genetic Ablation of Soluble TNF Does Not Affect Lesion Size and Functional Recovery after Moderate Spinal Cord Injury in Mice |
| title_fullStr | Genetic Ablation of Soluble TNF Does Not Affect Lesion Size and Functional Recovery after Moderate Spinal Cord Injury in Mice |
| title_full_unstemmed | Genetic Ablation of Soluble TNF Does Not Affect Lesion Size and Functional Recovery after Moderate Spinal Cord Injury in Mice |
| title_short | Genetic Ablation of Soluble TNF Does Not Affect Lesion Size and Functional Recovery after Moderate Spinal Cord Injury in Mice |
| title_sort | genetic ablation of soluble tnf does not affect lesion size and functional recovery after moderate spinal cord injury in mice |
| url | http://dx.doi.org/10.1155/2016/2684098 |
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