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.
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 humanskin diseases.
Authors: Brian G Engelhardt; Sophie Paczesny; Dae Kwang Jung; Etienne Daguindau; Madan Jagasia; Bipin N Savani; Wichai Chinratanalab; Robert F Cornell; Stacey Goodman; John P Greer; Adetola A Kassim; Salyka Sengsayadeth; Sandra M Yoder; Michael T Rock; James E Crowe Journal: Haematologica Date: 2016-01-27 Impact factor: 9.941
Authors: Jennifer L Barnas; Michelle R Simpson-Abelson; Sandra J Yokota; Raymond J Kelleher; Richard B Bankert Journal: Cancer Microenviron Date: 2010-03-31
Authors: Mandi Wiley; Kristin R Sweeney; Denise A Chan; Kevin M Brown; Curtis McMurtrey; Eric W Howard; Amato J Giaccia; Ira J Blader Journal: J Biol Chem Date: 2010-06-25 Impact factor: 5.157
Authors: Kenneth Friedman; Alexander S Brodsky; Shaolei Lu; Stephanie Wood; Anthony J Gill; Kara Lombardo; Dongfang Yang; Murray B Resnick Journal: Mod Pathol Date: 2016-03-11 Impact factor: 7.842
Authors: Irina V Pinchuk; Jamal I Saada; Ellen J Beswick; Gushyalatha Boya; Sumin M Qiu; Randy C Mifflin; Gottumukkala S Raju; Victor E Reyes; Don W Powell Journal: Gastroenterology Date: 2008-07-17 Impact factor: 22.682