Induction of transcription factor AP-2 by cytokines and prostaglandins in cultured mesangial cells.
OBJECTIVE
Activator protein-2 (AP-2) is an important transcription factor for activation of growth- and inflammatory-associated genes. To detect AP-2 in the mesangium, the expression level of AP-2 was examined in cultured mesangial cells in response to various cytokines and prostaglandins. The level was also observed in kidney tissue samples obtained from patients with proteinuria and from a rat nephrosis model.


METHODS
AP-2 was immunohistochemically detected with a specific antibody. The expression level was analyzed by immunoblotting. Human tissue samples were obtained from patients with proteinuria. Kidney samples were also obtained from rats with puromycin aminonucleoside-induced nephrosis.


RESULTS
Pro-inflammatory cytokines, such as IL-6, IL-1 and IL-2, but not TNF-alpha, induced AP-2 expression in a time- and dose-dependent manner in cultured mesangial cells. PGE(2) and PGI(2) also induced AP-2 expression, while PGF(2 alpha) failed to induce this protein. High expression levels of AP-2 were observed in different cell types including mesangial cells of kidney samples from patients with proteinuria. Similar results were obtained from the rat nephrosis model.


CONCLUSIONS
These findings demonstrate that the primary cytokines induce AP-2 protein in mesangial cells. AP-2 may act as a transcription factor to produce additional cytokines and growth-associated gene products, suggesting an important role for AP-2 for the function of mesangial cells in glomerular disorders.
Suyama
K
K
Department of Biomolecular Sciences, Fukushima Medical University School of Medicine, Fukushima, Japan.
Kabuyama
Y
Y
Suzuki
S
S
Kawasaki
Y
Y
Suzuki
J
J
Suzuki
H
H
Homma
Y
Y
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005920:Glomerular Mesangium / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D009401:Nephrosis / Q000473:pathology; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000096:biosynthesis*
D016207:Cytokines; D004268:DNA-Binding Proteins; D011453:Prostaglandins; D050656:Transcription Factor AP-2; D014157:Transcription Factors