دورية أكاديمية
أعرض في EDS

Surfen, a proteoglycan binding agent, reduces inflammation but inhibits remyelination in murine models of Multiple Sclerosis.

التفاصيل البيبلوغرافية
العنوان: Surfen, a proteoglycan binding agent, reduces inflammation but inhibits remyelination in murine models of Multiple Sclerosis.
المؤلفون: Warford JR; Department of Pathology, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, PO Box 15000, Halifax, NS, B3H 4R2, Canada., Lamport AC; Department of Pathology, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, PO Box 15000, Halifax, NS, B3H 4R2, Canada., Clements DR; Department of Pathology, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, PO Box 15000, Halifax, NS, B3H 4R2, Canada., Malone A; Department of Pathology, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, PO Box 15000, Halifax, NS, B3H 4R2, Canada., Kennedy BE; Department of Pathology, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, PO Box 15000, Halifax, NS, B3H 4R2, Canada., Kim Y; Department of Pathology, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, PO Box 15000, Halifax, NS, B3H 4R2, Canada., Gujar SA; Department of Pathology, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, PO Box 15000, Halifax, NS, B3H 4R2, Canada., Hoskin DW; Department of Pathology, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, PO Box 15000, Halifax, NS, B3H 4R2, Canada.; Department of Microbiology and Immunology, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, PO Box 15000, Halifax, NS, B3H 4R2, Canada., Easton AS; Department of Pathology, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, PO Box 15000, Halifax, NS, B3H 4R2, Canada. Alexander.Easton@dal.ca.
المصدر: Acta neuropathologica communications [Acta Neuropathol Commun] 2018 Jan 04; Vol. 6 (1), pp. 4. Date of Electronic Publication: 2018 Jan 04.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101610673 Publication Model: Electronic Cited Medium: Internet ISSN: 2051-5960 (Electronic) Linking ISSN: 20515960 NLM ISO Abbreviation: Acta Neuropathol Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2013]-
مواضيع طبية MeSH: Encephalomyelitis, Autoimmune, Experimental/*drug therapy , Immunologic Factors/*pharmacology , Inflammation/*drug therapy , Remyelination/*drug effects , Urea/*analogs & derivatives, Animals ; Bone Marrow/drug effects ; Bone Marrow/pathology ; Bone Marrow/physiology ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/pathology ; CD4-Positive T-Lymphocytes/physiology ; Cells, Cultured ; Chemokines/metabolism ; Corpus Callosum/drug effects ; Corpus Callosum/pathology ; Corpus Callosum/physiopathology ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Encephalomyelitis, Autoimmune, Experimental/physiopathology ; Female ; Immunologic Factors/administration & dosage ; Inflammation/pathology ; Inflammation/physiopathology ; Macrophages/drug effects ; Macrophages/pathology ; Macrophages/physiology ; Mice, Inbred C57BL ; Proteoglycans/metabolism ; RNA, Messenger/metabolism ; Remyelination/physiology ; Spinal Cord/drug effects ; Spinal Cord/pathology ; Spinal Cord/physiopathology ; Urea/adverse effects ; Urea/pharmacology
مستخلص: Proteoglycans are promising therapeutic targets in Multiple Sclerosis (MS), because they regulate many aspects of the immune response. This was studied using surfen, an agent that binds both heparan sulphate proteoglycans (HSPGs) and chondroitin sulphate proteoglycans (CSPGs). Initial cell culture work on bone marrow derived macrophages (BMDMs) found that surfen reduced concentrations of the chemokines CCL2, CCL4 and CCL5, with reduced messenger (m)RNA expression for Tumor Necrosis Factor, IL-6, IL-1β and inducible nitric oxide synthase. These data were further explored using Experimental Autoimmune Encephalomyelitis (EAE) in mice. Surfen reduced clinical signs during EAE when administered from disease onset, and reduced infiltration by CD4 positive T cells and macrophages into the central nervous system. These mice also showed reduced mRNA expression for the chemokines CCL3 and CCL5, with reduced concentrations of CCL2, CCL3 and CCL5. During EAE, surfen treatment induced a persistent increase in Interleukin (IL)-4 concentrations which may enhance T helper 2 responses. During EAE, surfen treatment reduced mRNA expression for HSPGs (NDST1, agrin, syndecan-4, perlecan, serglycin, syndecan-1) and the CSPG versican. By contrast, surfen increased mRNA expression for the CSPG aggrecan, with no effect on neurocan. During EAE, significant positive correlations were found between mRNA expression and clinical score for syndecan-4, serglycin and syndecan-1 and a significant negative correlation for aggrecan. These correlations were absent in surfen treated mice. Repair in the later stages of MS involves remyelination, which was modeled by injecting lysolecithin (lysophosphatidylcholine, LPC) into mouse corpus callosum to create regions of demyelination. When surfen was injected 2 days after LPC, it delayed remyelination of the lesions, but had no effect when injected 7 days after LPC. The delayed remyelination was associated with local increases in CSPG expression. Therefore surfen suppresses inflammation but inhibits remyelination in these models. A mechanism in common may be increased CSPG expression.
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معلومات مُعتمدة: 130574 Canada CIHR; 2017-05339 International Natural Sciences and Engineering Research Council of Canada; 34609 International Dalhousie Medical Research Foundation
فهرسة مساهمة: Keywords: Experimental autoimmune encephalomyelitis; Lysolecithin; Multiple sclerosis; Proteoglycan; Surfen
المشرفين على المادة: 0 (Chemokines)
0 (Immunologic Factors)
0 (Proteoglycans)
0 (RNA, Messenger)
08T7936572 (aminoquinuride)
8W8T17847W (Urea)
تواريخ الأحداث: Date Created: 20180106 Date Completed: 20180918 Latest Revision: 20181113
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5755315
DOI: 10.1186/s40478-017-0506-9
PMID: 29301568
قاعدة البيانات: MEDLINE
الوصف
تدمد:2051-5960
DOI:10.1186/s40478-017-0506-9