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Multiple Sclerosis
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Autoantigen-pulsed dendritic cells constitute a beneficial cytokine and growth factor network in ameliorating experimental allergic encephalomyelitis

Xuan Liu

Division of Neuroimmunology, Neurotec Department, Karolinska Institute, 14183 Huddinge, Stockholm, Sweden, Institute of Biomedical Sciences, Ruijin Hospital, Shanghai Second Medical University, PR China

Carolina Ciumas

Division of Neuroimmunology, Neurotec Department, Karolinska Institute, 14183 Huddinge, Stockholm, Sweden

Yu-Min Huang

Division of Neuroimmunology, Neurotec Department, Karolinska Institute, 14183 Huddinge, Stockholm, Sweden

Knut R Steffensen

Department of Biosciences, Karolinska Institute, 14157 Huddinge, Stockholm, Sweden

Hong Lian

Division of Neuroimmunology, Neurotec Department, Karolinska Institute, 14183 Huddinge, Stockholm, Sweden

Hans Link

Division of Neuroimmunology, Neurotec Department, Karolinska Institute, 14183 Huddinge, Stockholm, Sweden

Bao-Guo Xiao

Division of Neuroimmunology, Neurotec Department, Karolinska Institute, 14183 Huddinge, Stockholm, Sweden, Institute of Neurology, Fudan University, Shanghai, PR China, Bao-guo.Xiao{at}neurotec.ki.se

Injection of myelin basic protein (MBP)-pulsed dendritic cells (DC) into healthy rats, as we reported before and observed in this study, did not induce clinical experimental allergic encephalomyelitis (EAE), but effectively protected the rats from subsequent EAE induction. The mechanisms by which MBP-pulsed DC mediate immune protection are not completely understood. In the present study, we mainly explored the dynamic change of cytokine and growth factor mRNA expression in spinal cords after subcutaneous injection of MBP-pulsed and unpulsed DC. The expression of interleukin (IL)-1, interferon-g and tumour necrosis factor-a as well as programmed death ligand (PDL)-1, PDL-2, signal transducer and activator of transcription (STAT)4, STAT6, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinases (TIMP)-2 was increased on day 0 postimmunization (p.i.). The increase of IL-12 expression was observed on day 7 p.i., while the increase of IL-10 expression mainly occurred on day 14 p.i. Except downregulation of insulin-like growth factor-1, the expression of brain-derived neurotrophic factor, ciliary neurotrophic factor, fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-B/C as well as nerve growth factor receptor (NGF-R), FGF receptor, PDGF-R-a and b was elevated on day 0 p.i., while the increase of TIMP and NGF was observed on days 0 and 7 p.i. There were no significant differences on MMP-2, spinal cord-derived growth factor and PDGF-A mRNA expression. In line with the suppression of EAE induced by MBP-pulsed DC, the dynamic change of cytokines and growth factors in spinal cords should constitute a beneficial microenvironment against EAE.

Key Words: cytokine • dendritic cells • experimental allergic encephalomyelitis • growth factor • inflammation

Multiple Sclerosis, Vol. 11, No. 4, 381-389 (2005)
DOI: 10.1191/1352458505ms1180oa


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