Pleiotrophin regulates functional heterogeneity of microglia cells in EAE animal models of multiple sclerosis by activating CCr-7/CD206 molecules and functional cytokines

摘要

Multiple sclerosis (MS) is a neurodegenerative and immune-mediated disorder that characterizes by demyelination and neuro-inflammation. This study aimed to investigate the effects of pleiotrophin (PTN) on treatment of early injuries of white matter of MS patients. Experimental autoimmune encephalomyelitis (EAE) animal models were established by injecting 200 μg myelinoligodendrocyte glyeoprotein 33-35 (MOG35-55) and were divided into PTN+MOG group and PBS+MOG group. Meanwhile, normal mice group was assigned as control group (NC group). Immunofluorescence double label was used to examined co-expression of molecules. LV5-PTN and LV3-siPTN were established and transfected into microglia cells. All brain imaging data was acquired with MRI scanner. Quantitative real-time RT-PCR (qRT-PCR) and western blot were used to evaluate mRNA and protein expression, respectively. Lesion sites mainly appeared in NAWM of bilateral occipital lobes in EAE models. PTN treatment significantly enhanced CCr7 and reduced CD206 expression compared to PBS+MOG group (P<0.05). PTN participated in mitogen-activated protein kinase (MAPK) signaling pathway in EAE models. PTN treatment significantly regulated levels of functional cytokines in both M1 and M2 type microglia cells compared to PBS+MOG group (P<0.05). LV5-PTN and LV3-siPTN transfection modulated levels of PTN and MAPK molecule in microglia cells undergoing treatment of M1 or M2 inducer. PTN strengthened M1/M2 transformation by regulating functional cytokines. In conclusion, PTN regulated functional heterogeneity of microglia cells in EAE animal models of MS by activating CCr-7/CD206 molecules and functional cytokines. PTN could be considered as a promising candidate molecule for treating early injuries of white matter of patients with MS.