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


CONCLUSIONS
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.
Lee
Sang-Keun
SK
Institute of Traditional Medicine and Bioscience, Daejeon University, 96-3 Yongun-dong, Daejeon 300-716, Republic of Korea.
Seo
Sam-Hwa
SH
Kim
Byoung-Soo
BS
Kim
Chang-Deok
CD
Lee
Jeung-Hoon
JH
Kang
Jung-Soo
JS
Maeng
Pil Jae
PJ
Lim
Jong-Soon
JS
D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000235:genetics*; D060890:B7-H1 Antigen; D002478:Cells, Cultured; D003872:Dermatitis / Q000503:physiopathology*; D020405:Dermis / Q000166:cytology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017353:Gene Deletion; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005816:Genetic Complementation Test; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis
D015703:Antigens, CD; D000970:Antineoplastic Agents; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010455:Peptides; D012333:RNA, Messenger; D007371:Interferon-gamma; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases