SOCS1 Regulates the Immunomodulatory Roles of MSCs on B Cells.

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.

Puerarin prevents vascular endothelial injury through suppression of NF-κB activation in LPS-challenged human umbilical vein endothelial cells.

OBJECTIVE: In the present study, we aimed to explore the effects of puerarin on vascular endothelial cell injury induced by lipopolysaccharide (LPS) and its underlying mechanisms. METHODS: The cell viability and morphological changes were assessed using the cell counting kit-8 (CCK-8) assay and 4´,6-diamidino-2-phenylindole (DAPI) staining, respectively. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), monocyte/macrophage chemotactic protein-1 (MCP-1), IL-8, intercellular cell adhesion molecule-1 (ICAM-1), thrombomodulin (TM) and plasminogen activator inhibitor-1 (PAI-1) in cell culture supernatant were determined by the enzyme-linked immunosorbent assay (ELISA). The neutrophils adhesion to endothelial cells were examined by myeloperoxidase activity assay. The nuclear translocation of nuclear factor-κB p65 (NF-κB p65) was assessed by immunofluorescence analysis. RESULTS: Compared with the control group, LPS challenge significantly injured human umbilical vein endothelial cells (HUVECs) and increased the levels of TNF-α, IL-1ß, MCP-1, IL-8, ICAM-1, TM and PAI-1 in the cell culture supernatants. The neutrophils adhesion to endothelial cells were significantly increased in LPS-challenged HUVECs. Moreover, LPS challenge increased the nuclear translocation of NF-κB p65. However, puerarin pre-treatment attenuated the vascular endothelial injury and reduced the levels of TNF-α, IL-1ß, MCP-1, IL-8, ICAM-1, TM and PAI-1 in cell supernatants of LPS-challenged HUVECs. In addition, the neutrophils adhesion to HUVECs induced by LPS were also decreased by puerarin pre-treatment. Furthermore, puerarin pre-treatment reduced the nuclear translocation of NF-κB p65 elicited by LPS. CONCLUSIONS: Puerarin prevented LPS-induced vascular endothelial injury, the mechanism of which might be related to the suppression of NF-κB activation and subsequently altered levels of inflammatory factors and coagulation-related factors.

[Analysis on mutations of GJB2 gene in Chinese population].

OBJECTIVE: To determine the prevalence and types of GJB2 mutations and to investigate the genetic mechanism in Chinese autosomal recessive deafness. METHODS: The subjects were four Chinese pedigrees (39 individuals) and 50 normal adults. GJB2 was amplified by PCR. The products were digested with restriction enzyme Apa I, then sequenced. RESULTS: Homozygous deletion C at position 232-235 of GJB2 (235delC),which resulted in frameshift mutation, was found in four affected individuals of two pedigrees; the compound heterozygous deletions (235delC/232G to A) were found in two affected individuals in one pedigree. One carrier with 235delC was found in normal controls (1% allele). Two kinds of polymorphisms 79G to A(V27I) and 3 41A to G(E114G) were found in both affected and normal controls. The frequencies of allele for 79G to A and 341A to G in normal controls were 30%, 21%, respectively. CONCLUSION: 235delC mutation of GJB2 was related with Chinese autosomal recessive deafness, and the 232G to A(Ala78Thr) missense mutation was found to be a novel mutation.