Objectives To investigate the expression of TGF-?receptors and signaling protein SMADs mRNA in psoriatic lesional and nonlesional skin,and to analyze their role in the pathogenesis of psoriasis.Methods Expression of TGF-?receptorⅠ,TGF-?receptorⅡmRNA and different SMADs(SMAD2,3,4,6,7)mRNA was investigated by real time PCR method in lesional and nonlesional skin of13psoriatic patients and10normal controls.Results The mRNA expression of TGF-?receptors and all kinds of SMADs was significantly down-regulated in psoriatic lesional skin compared with normal skin con-trols(P0.05).Conclusions There is down-regulated TGF-?pathway in psoriatic lesional skin,which may further indicate that lack of TGF-?mediated growth inhibition might play an important role in the pathogenesis of psoriasis.

Objective The critical role of infiltrating T cells in the pathogenesis of psoriasis is now well established. In order to determine whether circulating T cells from patients with psoriasis were also involved in the disease process, the authors investigated the biological behavior as studied by chemotactic activity of T cells in patients with psoriasis. Methods A 48 microchemotaxis chamber was employed to determine T-cell chemotaxis activity. In addition, the expression of T cell activation markers such as HLA-DR and interleukin 2 receptor were analysed with fluorescence activated cell sorting technique and serum IL-8 level was measured with ELISA methods. Forty-five patients with psoriasis (23 patients with severe psoriasis and 22 with mild psoriasis) and 21 patients with atopic dermatitis were investigated. For comparison, T-lymphocytes from 20 healthy controls were tested equally.Results T-cell chemotactic responses were significantly decreased in patients with severe psoriasis and atopic dermatitis as compared to healthy controls. Increased expression of activation markers such as HLA-DR and interleukin 2 receptor were demonstrated in circulating T cells from psoriatic patients and atopic dermatitis patients in comparison to healthy controls. Serum IL-8 level was significantly increased in patients with psoriasis and atopic dermatitis. Conclusions Circulating T cells in patients with severe psoriasis show abnormal in vitro chemotactic response to IL-8. Furthermore, the in vivo activation state of T lymphocytes in these patients and increased level of serum IL-8 seemed to be associated to their decreased in vitro T-cell chemotactic responses.

Objective To characterize the mRNA expression of CXC chemokine IL-8, CC chemokine monocyte chemothractant protein-1 (MCP-1) and regulated on activation,normal T cell expressed and secreted (RANTES), and a newly defined DC chemokine DC- CK1 as well as the expression of IL-8 receptor, MCP-1 receptor and RANTES receptor in human monocyte derived dendritic cells (MoDCs).The migratory responsiveness of MoDC to IL-8, MCP-1 and RANTES was alsso studied. Methods In vitro generated MoDCs were obtained by differentiating monocytes in the presence of GM-CSF and IL-4 for 5 days. The time course of RNA expression was analyzed by RT-PCR and migratoly ability was assessed by a micromultiwell chemotaxis chamber assay. Results IL-8, MCP-1, RANTES and their corres ponding receptors were consistently expressed in MoDCs. DC-CK-1 expression was detectable efter 48 hours of differentiation. MoDC selectively migrated in response to MCP-1 and RANTES but not to IL-8 though transcripts of IL-8 receptor were present. Conclusion Because the capacity of dendritic cells to initiate immune responses depends on their specialized migratory and tissue homing properties, the expression of chemokines and their receptors along with the migratory responsiveness to chemokines of MoDC in our study suggests a potential role of chemokines in the interaction between dendritic cells and T cells and the induction of immune responses.

OBJECTIVE: To investigate the effect of anti-psoriatic drug fumaric acid esters (FAE) on the differentiation of dendritic cells (DC). METHODS: Dendritic cells were obtained by differentiating human monocytes in vitro. Flow cytometry was used to analyse the effect of FAE on cell surface expression of CD1a, CD14, CD40, CD80, CD86 and HLA-DR by monocyte-derived dendritic cells (MoDC). Mixed lymphocyte reaction (MLR) was made to demonstrate the influence of FAE on T cell stimulatory activity of MoDC. RESULTS: Dimethylfumarate and methylhydrogenfumarate-calcium-salt (0.01 approximate, equals 100 mg/L) inhibited MoDC differentiation as well as reducing the capacity of MoDC to stimulate lymphocytic proliferation in MLR. CONCLUSION: The mode of action of FAE in pso riasis may be mediated by inhibition of DC differentiation.