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Background and Objectives@#Mesenchymal stem cells (MSCs) have immunomodulatory function and participate in the pathogenesis of many immunoregulation-related diseases, including psoriasis. Previously, we found that MSCs from psoriatic lesions overexpress the proinflammatory microRNA, miR-155 and exhibit a decreased immunosuppressive capacity. But the origin of these aberrant characteristics is still not clear. To investigate whether inflammatory cytokines in serum and peripheral blood mononuclear cells (PBMCs) from psoriatic patients can regulate the expression patterns of immunoregulation-related cytokines and the immunoregulation function of MSCs. @*Methods@#and Results: Normal dermal mesenchymal stem cells (nDMSCs) were treated with serum or PBMCs derived from patients with psoriasis or healthy donors. Expression of miR-155 and immunoregulation-related genes in each MSCs were measured using real-time PCR or western-blot. Meanwhile, the immunosuppressive capacity of DMSCs was evaluated by its inhibitory ability on proliferation of activated PBMCs. Compared to control serum, psoriatic serum significantly increased the expression levels of miR-155 (27.19±2.40 vs. 3.51±1.19, p<0.001), while decreased TAB2 expression (0.28±0.04 vs. 0.72±0.20, p<0.01) in DMSCs. Expression levels of immunoregulation-related genes such as PGE2, IL-10, and TLR4 were also markedly down-regulated following the psoriatic serum treatment. Those DMSCs treated with healthy serum could inhibit PBMC proliferation, while those psoriatic serum-treated DMSCs could not inhibit PBMC proliferation effectively. @*Conclusions@#Psoriatic serum up-regulate the expression of miR-155, down-regulate the expression of immunoregulation- related genes (PGE2, IL-10, and TLR4) in DMSCs, and along with the inhibition of the immunosuppressive function of MSCs.
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Background and Objectives@#Psoriasis is a chronic inflammatory skin disease, which the mechanisms behind its initiation and development are related to many factors. DMSCs (dermal mesenchymal stem cells) represent an important member of the skin microenvironment and play an important role in the surrounding environment and in neighbouring cells, but they are also affected by the microenvironment. We studied the glucose metabolism of DMSCs in psoriasis patients and a control group to reveal the relationship among glucose metabolism, cell proliferation activity，and VEC (vascular endothelial cell) differentiation in vitro, we demonstrated the biological activity and molecular mechanisms of DMSCs in psoriasis. @*Methods@#and Results: We found that the OCR of DMSCs in psoriatic lesions was higher than that in the control group, and mRNA of GLUT1 and HK2 were up-regulated compared with the control group. The proliferative activity of DMSCs in psoriasis was reduced at an early stage, and mRNA involved in proliferation, JUNB and FOS were expressed at lower levels than those in the control group. The number of blood vessels in psoriatic lesions was significantly higher than that in the control group (p＜0.05), which the mRNA of VEC differentiation, CXCL12, CXCR7, HEYL and RGS5 tended to be increased in psoriatic lesions compared to the control group, in addition to Notch3. @*Conclusions@#We speculated that DMSCs affected local psoriatic blood vessels through glucose metabolism, and the differentiation of VECs, which resulted in the pathophysiological process of psoriasis.
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Objective To assess the preferential expressions of peripheral blood T cell receptor beta chain variable region (TRBV) subfamilies in patients with psoriasis vulgaris(PV), and to estimate their role in the pathogenesis of psoriasis. Methods Thirty-three upstream primers were designed to target the human functional TRBV genes, downstream primers to target the common T cell receptor beta constant (TRBC) gene,with T cell receptor alpha constant (TRAC) gene as the internal reference. Total RNA was extracted from the peripheral blood T cells of 10 health human controls and 10 patients with PV, and transcribed into cDNA.Then, TRBV genes were amplified by real-time fluorescence quantitative PCR (RFQ-PCR) and the fluorescence intensity of each samples was detected. The expression levels of TRBV genes in the control group were used to calculate the cut-off values (mean expression levels of TRBV subfamilies in the 10 normal controls + 3 standard deviations). When the expression level of a TRBV subfamily from patients with PV was equal to or higher than the cut-off value, it was considered as the preferentially expressed TRBV subfamily. Results The threshold cycle (Ct) value varied from 21 to 24 for TRAC gene. The difference in the Ct value between TRBV subfamily genes and TRAC gene in patients with PV was 2.98 for TRBV2 gene, 3.24 for TRBV5-7 gene, 2.52 for TRBV6-6/6-9 gene, 2.04 for TRBV 12 gene, 3.56 for TRBV 24 gene, and 4.12 for TRBV 29 gene, and the expression levels of these subfamily genes were significantly higher than those in the normal controls (all P ＜ 0.05). According to the above standard, TRBV6-6/6-9, TRBV12 and TRBV29 were considered to be preferentially expressed subfamilies. Conclusions There is a preferential expression of TRBV gene subfamilies in peripheral blood of patients with psoriasis vulgaris, which may play a vital role in the abnormal T cell-mediated immune responses in psoriasis.
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Objective To study the expressions of Notch receptors (Notch1 and 2) and target gene Hes-1 in bone marrow CD34+ cells from patients with psoriasis. Methods CD34+ cells were isolated from the bone marrow of 12 patients with psoriasis and 19 normal human controls. Western blot was conducted to detect the expressions of Notchl, Notch2 and Hes-1 proteins in CD34+ cells, with the house-keeping gene β-actin as an internal reference. Results In contrast with normal controls, a significant increment was observed in the expressions of Notch1 and Hes-1 proteins in psoriatic patients (0.9488 ± 0.3221 vs. 0.6693 ± 0.1465, 0.8579 ±0.3729 vs. 0.5728 ± 0.1787, both P ＜ 0.05). No significant difference was observed in the expression of Notch2 between psoriatic patients and normal controls (0.7568 ± 0.3461 vs. 0.8312 ± 0.2887, P ＞ 0.05).Conclusion The overexpression of Notch1 and Hes-1 may be associated with the low proliferation activity of psoriatic hematopoietic cells.
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Objective:To reveal the relation between RUNX1 and hematopoietic cells by examination of the expression of RUNX1 and its target gene SLC9A3R1 in bone marrow CD34+ cells from patients with psoriasis,as well as the RUNX1 linkage locus between SLC9A3R1 and NAT9.Methods:Bone marrow CD34+ cells were isolated from psoriatic patients and normal persons by immunomagnetic cell selection.Expression of mRNA for RUNX1 and SLC9A3R1 were analyzed using reverse transcriptase-polymerase chain reaction(RT-PCR),the RUNX1 linkage locus between SLC9A3R1 and NAT9 was detected.Results:The positive frequency of RUNX1 in bone marrow CD34+ cells from patients with psoriasis was lower than in normal controls(P