Nasal administration of transforming growth factor-β1 induces dendritic cells and inhibits protracted-relapsing experimental allergic encephalomyelitis

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.

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IL-4 is a differentiation factor for transforming growth factor-β secreting Th3 cells and oral administration of IL-4 enhances oral tolerance in experimental allergic encephalomyelitis

European Journal of Immunology ◽

10.1002/(sici)1521-4141(199809)28:09<2780::aid-immu2780>3.0.co;2-j ◽

1998 ◽

Vol 28 (9) ◽

pp. 2780-2790 ◽

Cited By ~ 154

Author(s):

Jun-ichi Inobe ◽

Anthony J. Slavin ◽

Yoshinori Komagata ◽

Youhai Chen ◽

Liming Liu ◽

...

Keyword(s):

Growth Factor ◽

Oral Administration ◽

Experimental Allergic Encephalomyelitis ◽

Oral Tolerance ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Allergic Encephalomyelitis ◽

Differentiation Factor ◽

Experimental Allergic

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Nasal administration of transforming growth factor-β1 induces dendritic cells and inhibits protracted-relapsing experimental allergic encephalomyelitis

Multiple Sclerosis Journal ◽

10.1177/135245859900500308 ◽

1999 ◽

Vol 5 (3) ◽

pp. 184-191 ◽

Cited By ~ 16

Author(s):

Mikio Ishikawa ◽

Yuxuen Jin ◽

Hong Guo ◽

Hans Link ◽

Bao-Guo Xiao

Keyword(s):

Dendritic Cells ◽

Growth Factor ◽

Mononuclear Cells ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Nasal Administration ◽

Low Doses ◽

T Cell Apoptosis ◽

The Central Nervous System ◽

Tgf Β1

Cytokines have a crucial role in initiation and perturbation of EAE that represents an animal model of multiple sclerosis (MS). Administration of transforming growth factor-β1 (TGF-β1) to EAE mice improves clinical EAE and prevents relapses by unknown mechanisms. Administering low doses of TGF-β1 nasally, we confirmed that TGF-β1 inhibited development and relapse of protracted-relapsing EAE (PR-EAE) in DA rats. Infiltration of CD4+ T-cells and macrophages within the central nervous system was clearly reduced, while proliferation and IFN-g secretion of mononuclear cells (MNC) was augmented in TGF-β1-treated EAE rats compared to PBS-treated control EAE rats. TGF-β1 administered nasally also increased nitric oxide production and CD4+ T cell apoptosis. TGF-β1 treated rats showed augmented proliferation of dendritic cells (DC) compared to MNC. These data imply that low doses of TGF-β1 given by the nasal route prevent PR-EAE and upregulate DC functions that may be involved for disease prevention.

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