Cyclosporin A Affects Signaling Events Differentially in Human Gingival Fibroblasts

Autor: H. Bharath, A. Bostrom, A. S. Narayanan, A. Saulewicz
Rok vydání: 2005
Předmět:
0301 basic medicine
Cell signaling
MAP Kinase Kinase 4
T-Lymphocytes
p38 mitogen-activated protein kinases
Gingiva
Lymphocyte Activation
p38 Mitogen-Activated Protein Kinases
03 medical and health sciences
0302 clinical medicine
Western blot
Cyclosporin a
medicine
Humans
Extracellular Signal-Regulated MAP Kinases
General Dentistry
Transcription factor
Cells
Cultured

Mitogen-Activated Protein Kinase Kinases
Platelet-Derived Growth Factor
Mitogen-Activated Protein Kinase 3
NFATC Transcription Factors
medicine.diagnostic_test
biology
Tumor Necrosis Factor-alpha
Kinase
JNK Mitogen-Activated Protein Kinases
NF-kappa B
Nuclear Proteins
NFAT
030206 dentistry
Fibroblasts
Molecular biology
DNA-Binding Proteins
Transcription Factor AP-1
030104 developmental biology
Cyclosporine
Cancer research
biology.protein
Immunosuppressive Agents
Platelet-derived growth factor receptor
Signal Transduction
Transcription Factors
Zdroj: Journal of Dental Research. 84:532-536
ISSN: 1544-0591
0022-0345
DOI: 10.1177/154405910508400609
Popis: Gingival overgrowth is a common side-effect of the administration of cyclosporin A (CSA), phenytoin, and calcium blockers. To identify the signaling mechanisms possibly involved in the overgrowth, we examined how CSA affects the activities of MAP kinases and transcription factors in human gingival fibroblasts (HGF). The HGF were treated with CSA and TNF-alpha or PDGF. DNA-binding activity of NFAT, NFkappaB, and AP-1 transcription factors was determined by gel shift assay, and JNK, p38, and ERK1 and ERK2 activation was assessed by Western blot analysis of immunoprecipitates. The CSA inhibited NFAT, NFkappaB, and p38 and JNK activities; however, ERK1 and ERK2 were not affected significantly. AP-1 activity increased approximately 4.5-fold. Our results indicate that CSA affects signaling molecules in HGF differently from other cell types, and that a CSA-induced increase in AP-1 activity may affect the expression of fibrogenic molecules in gingiva and promote gingival overgrowth.
Databáze: OpenAIRE