ABSTRACT
BACKGROUND AND OBJECTIVES: The effective use of MSCs for the treatment of some B cell-mediated immune diseases is quite limited. The main reason is that the immunomodulatory effects of mesenchymal stem cells (MSCs) on B cells are unclear, and their underlying mechanisms have not been fully explored. METHODS AND RESULTS: By co-culturing B cells with MSCs without (MSC/CTLsh) or with suppressor of cytokine signaling 1 (SOCS1) knockdown (MSC/SOCS1sh), we found that MSCs inhibited B cell proliferation, activation and terminal differentiation. Remarkably, the highest inhibition of B cell proliferation was observed in MSC/SOCS1sh co-culture. Besides, MSC/SOCS1sh reversed the inhibitory effect of MSCs in the last stage of B cell differentiation. However, MSC/SOCS1sh had no effect on inhibiting B cell activation by MSCs. We also showed that IgA+ B cell production was significantly higher in MSC/SOCS1sh than in MSC/CTLsh, although no difference was observed when both MSCs co-cultures were compared to isolated B cells. In addition, MSCs increased PGE2 production after TNF-α/IFN-γ stimulation, with the highest increase observed in MSC/SOCS1sh co-culture. CONCLUSIONS: Our results highlighted the role of SOCS1 as an important new mediator in the regulation of B cell function by MSCs. Therefore, these data may help to develop new treatments for B cell-mediated immune diseases.
ABSTRACT
Hepatocyte growth factor (HGF) and its receptor c-Met play pivotal roles in post-traumatic regeneration of the nervous system. However, following peripheral nerve injury, the role and regulation of the HGF/c-Met system is less clear. Therefore, using a sciatic nerve ligation (SNL) model, spatiotemporal changes in HGF and c-Met expression were detected in the dorsal root ganglions (DRGs) and lumbar spinal cords of adult rats. HGF expression following SNL was found to be significantly decreased in ipsilateral L4-L5 DRGs from day 3 to day 14, with the lowest levels of expression detected on days 5 and 7. In contrast, no significant change in HGF expression was detected in the lumbar spinal cords. c-Met expression in ipsilateral L4-L5 DRGs and within the ipsilateral dorsal horn was found to be significantly up-regulated following SNL, particularly from day 5 to day 14, with peak levels of expression detected on days 7 and 14. In contrast, c-Met levels following SNL consistently remained stable in the spinal ventral horn. These findings suggest that the HGF/c-Met system is spatiotemporally regulated by a unique pattern of signaling pathways induced by peripheral nerve injury, and these pathways have a role in promoting the survival of injured neurons, especially adult DRG sensory neurons.
Subject(s)
Ganglia, Spinal/metabolism , Gene Expression Regulation/physiology , Hepatocyte Growth Factor/metabolism , Proto-Oncogene Proteins c-met/metabolism , Sciatic Neuropathy/pathology , Spinal Cord/metabolism , Animals , Calcitonin Gene-Related Peptide/metabolism , Choline O-Acetyltransferase/metabolism , Disease Models, Animal , Functional Laterality , Glial Fibrillary Acidic Protein/metabolism , Hepatocyte Growth Factor/genetics , Male , Proto-Oncogene Proteins c-met/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Serotonin/metabolism , Time FactorsABSTRACT
OBJECTIVE: To demonstrate the spatial organization of neurons, astrocytes and vessels in rat brain. METHODS: Cerebral vascular was shown by vivi-perfusion with ink. Glial fibrillary acidic protein (GFAP) immunohistochemistry and nissl's staining were performed on the serial sections of frozen brain tissues. RESULTS: Astracytes distributed along the branches of blood vessels, and neurons in the region of the relatively rich blood vessels. Neurons and astrocytes presented regional distribution. CONCLUSION: This method can well indicate the spatial organization of neurovascular unit, the regional differences in the distribution may be related to physical activities and the corresponding adjustment function.