Immunoregulative effect of Fasudil on encephalomyelitic T cells in experimental autoimmune encephalomyelitis mice / 中南大学学报(医学版)
Journal of Central South University(Medical Sciences)
; (12): 225-232, 2016.
Article
in Zh
| WPRIM
| ID: wpr-815049
Responsible library:
WPRO
ABSTRACT
OBJECTIVE@#To explore the therapeutic effect of Fasudil-modified splenic mononuclear cells (MNCs) in experimental autoimmune encephalomyelitis (EAE) and the possible mechanisms.
@*METHODS@#C57BL/6 female mice were immunized with myelin oligodendrocyte glycoprotein peptide 35-55 to establish active immunity EAE model. Splenic MNCs were isolated on the 9th day after immunization and treated with or without Fasudil for 72 h in vitro. These cells were collected for analysis of the variance of T cell subtypes, the level of cytokines and the activity of Rho kinase (ROCK). MNCs (5×107 cells) were resuspended in 500 µL of phosphate buffer solution (PBS) and transferred into EAE model (intraperitoneal injection), which was divided into a PBS-MNCs group and a Fasudil-MNCs group. Changes of body weight and clinical symptom scores were observed.
@*RESULTS@#Splenic encephalitogenic MNCs from EAE mice on the 9th day after immunization could establish passive transfer EAE model. But Fasudil-treated MNCs did not trigger EAE development. Compared with the PBS-MNCs group, the loss of body weight was less in the Fasudil-MNCs group. The in vitro experiment indicated that Fasudil could suppress the activity of ROCK on MNCs (P<0.01), decrease the percentage of CD4+ T cells with the expression of interferon-γ (IFN-γ) and interleukin-17 (IL-17) (IFN-γ P<0.01; IL-17 P<0.05), while increase the secretion of CD4+ T cells with the expression of transforming growth factor-β (TGF-β) and IL-10 (all P<0.001) . Furthermore, Fasudil could inhibit the release of IL-17 (P<0.001) and enhance the level of IL-10 (P<0.05).
@*CONCLUSION@#Fasudil-modified cell therapy affects the occurrence and development of EAE by inhibiting the inflammatory reaction of helper T cell 1 (Th1) and Th17 while enhancing the immunoregulative effect of Th2.
Full text:
1
Index:
WPRIM
Main subject:
Spleen
/
T-Lymphocytes
/
Transforming Growth Factor beta
/
Interferon-gamma
/
Interleukin-10
/
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Interleukin-17
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Encephalomyelitis, Autoimmune, Experimental
/
Rho-Associated Kinases
/
Myelin-Oligodendrocyte Glycoprotein
Type of study:
Prognostic_studies
Limits:
Animals
Language:
Zh
Journal:
Journal of Central South University(Medical Sciences)
Year:
2016
Type:
Article