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

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.

• Authors: Sang-Keun Lee, Sam-Hwa Seo, Byoung-Soo Kim, Chang-Deok Kim, Jeung-Hoon Lee, Jung-Soo Kang, Pil Jae Maeng, Jong-Soon Lim
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 40 Issue 2 Pg. 95-103 (Nov 2005) ISSN: 0923-1811 [Print] Netherlands
• PMID: 16085391 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Antineoplastic Agents
• B7-1 Antigen
• B7-H1 Antigen
• CD274 protein, human
• Membrane Glycoproteins
• NF-kappa B
• Peptides
• RNA, Messenger
• Interferon-gamma
• Phosphatidylinositol 3-Kinases
• Extracellular Signal-Regulated MAP Kinases

Topics

• Antigens, CD
• Antineoplastic Agents (pharmacology)
• B7-1 Antigen (genetics)
• B7-H1 Antigen
• Cells, Cultured
• Dermatitis (physiopathology)
• Dermis (cytology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Fibroblasts (cytology, drug effects, physiology)
• Gene Deletion
• Gene Expression (drug effects, physiology)
• Genetic Complementation Test
• Humans
• Interferon-gamma (pharmacology)
• MAP Kinase Signaling System (drug effects, physiology)
• Membrane Glycoproteins (genetics)
• NF-kappa B (metabolism)
• Peptides (genetics)
• Phosphatidylinositol 3-Kinases (metabolism)
• Promoter Regions, Genetic (physiology)
• RNA, Messenger (analysis)