IFN-gamma regulates the expression of B7-H1 in dermal fibroblast cells

Summary: 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-γ 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-κB transcription factors mediate the induction of B7-H1 expression via the transient phosphorylation of ERK1/2 and PI3K when cells are stimulated by IFN-γ. Also, Specific destruction of the NF-κB binding site abolished the induction of the promoter activity by IFN-γ. 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-κB and MAPK and PI3K, that may play some important roles in inflammation process in human skin diseases. [Copyright &y& Elsevier]