ABSTRACT
BACKGROUND: Psoriasis is a chronic inflammatory skin disease that affects approximately 1~3% of the general population. OBJECTIVE: We performed cDNA microarray analysis with using the dendrimer labelling method to investigate the gene expression profile in the peripheral blood mononuclear cells (PBMCs) of psoriatic patients. METHODS: The peripheral blood mononuclear cells of 5 patients with psoriasis and 8 control subjects were used in the gene expression analyses of psoriasis. RESULTS: We identified 212 differentially expressed genes that showed at least a two-fold induction and/or reduction in psoriatic patients. Among those, 63 genes, including CD44, CD56 and IL7R, were induced, while 139 genes, including the sphingosine kinase 1 and p16-INK genes, were reduced in the psoriatic patients. CONCLUSION: We can speculate that these genes may have a role for the pathogenesis of psoriasis via their affecting different cellular functions. Our results suggest a possible mechanism by which activated immune cells migrate from the blood to the skin in psoriatic patients, and we provide novel putative targets for developing drugs to treat psoriasis.
ABSTRACT
BACKGROUND: Programmed cell death ligand 1 (B7-H1) was recently cloned in antigen presenting cells (APCs) and represents a third member of the B7 family. Thus, B7-H1 may be a novel target for clinical intervention in human inflammatory disease. OBJECTIVE: The aim of this study is to investigate the signal transduction mechanism and transcriptional regulation of B7-H1 expression in human dermal fibroblasts. METHODS: We performed reverse transcription PCR (RT-PCR) for the detection of mRNA expression, luciferase reporter assays with B7-H1 promoter constructs, and Western blot analysis. RESULTS: From RT-PCR analysis, IFN-gamma can induce the expression of B7-H1 mRNA in dermal fibroblast. This expression is similar to the results of luciferase reporter assay with B7-H1 promoter. Western blot analysis and EMSA revealed that NF-kappaB transcription factors mediate the induction of B7-H1 expression via the transient phosphorylation of ERK1/2 and PI3K when cells are stimulated by IFN-gamma. Also, Specific destruction of the NF-kappaB binding site abolished the induction of the promoter activity by IFN-gamma. CONCLUSION: Our data not only provides the first evidence to demonstrate that dermal fibroblast express the B7-H1 mRNA in the process of skin inflammation, but also suggests the involvement of NF-kappaB and MAPK and PI3K, that may play some important roles in inflammation process in human skin diseases.
