Expression Of IL-18 Bind Protein In Monocyte And Monocyte-drived Langerhans Cell Of Psoriasis

Psoriasis is an inflammatory disease with resultant hyperplasia and abnormal differentiation of epidermal keratinocytes, dilatation of capillary vessels in papillae of corium and infiltration and recruitment of inflammatory cells.There are more than 3 million patients with psoriasis in China while about 20 millions in the world. Usually patients are in the middle of the age and psoriasis has severe adverse impacts upon both patients' psychological health and social economic construction. So far the pathogenesis of psoriasis is not well understood, but it is considered to be associated with many factors such as abnormity of heredity, metabolism and neuropsychology. The disturbance of immune function plays a more important role in this disease. Today psoriasis has been generally regarded as a T-helper (Th) 1-dominated disease.Langerhans cells (LCs) are a kind of immature dendritic cells (DCs), residing in the superbasal layer of the epidermis. Their role in the pathogenesis of psoriasis has been gradually recognized. Human DCs and monocytes can secrete IL-12 and IL-18, which induce T cells including CD4+ and CD8+ and NK cells to produce IFN- Y . IFN- y reversely induces DCs and monocytes to secrete IL-18BP, then IL-18BP binds with IL-18 and depress the secretion of IFN- γ .So there forms the IL-18/IL-18BP negative feedback loop to regulate Thl cellular immune responses. Our previous study indicated there were abnormal levels of cytokines in the serum of psoriatic patients. In this study we found the level of IL-18BPa in the plasma of psoriatic patients is significantly lower than that of normal controls. The lowest level appears in the progression phase, but that in the regression phase is similar to normal controls. It is also found that the level of IL-18BPa has a negative correlation with PASI score. This finding indicates that IL-18BPa as an inhibitor decreases in the plasma of psoriatic patients. The abnormal IL-18/IL-18BP negative feedback loop will enhance Thl cellular immune responses, and this may play an important role in the pathogenesis of psoriasis.In vitro LCs can be obtained from the peripheral blood monocytes. At present monocytes are considered to be the precursors of LCs. IFN- y is secreted mainly by T cells and NK cells, while IL-18BP is produced chiefly by monocytes. In human, there exist at least four isoforms of IL-18BP. IL-18BPa and IL-18BPc have high affinity to neutralize IL-18, and then suppressing IFN-γ production. But IL-18BPband IL-18BPd, on the other hand, don't have such function. IL-18BPa and IL-18BPb can be both expressed in the peripheral blood monocytes. It is found that the plasma level of IL-18BPa in patients with psoriasis is lower than that in normal controls. In our study we investigated whether that is due to the abnormal synthess function of IL-18BP by monocytes in psoriatic patients. We found IL-12 induced peripheral blood mononuclear cells to express IFN-y mRNA and IL-18BPa mRNA both in psoriatic patients and normal controls, but there was no expression of IL-18BPb mRNA. TGF- {3 1 can suppress the expression of IL-18BPa mRNA by downregulating IFN-Y mRNA, and the expression of IFN-Y mRNA and IL-18BPa mRNA are significantly higher in psoriatic patients than in normal controls. This result proved further that there is Thl cellular immune responses in the psoriasis, that the IL-18/IL-18BP negative feedback loop exits and IL-18BPa mRNA expression was regulated by IFN- Y .The count of NIC cells by flow cytometer in psoriatic patients is siginificantly higher than in normal controls, probally associated with the increase of IFN- Y mRNA expression. Therefore, under the stimulation of IL-12, the high expression of IL-18BPa mRNA by monocytes of psoriatic patients is probally due to the upregulation of IFN- Y mRNA. After 24 hours stimulation of IL-12, the level of IL-18BPa in the supernatant of psoriatic peripheral blood mononuclear cells exhibits no significant difference from normal controls. The reason might be that the protein hasn't been produced sufficiently in 24 hours.