Induction of Transcription Factor AP-2 by Cytokines and Prostaglandins in Cultured Mesangial Cells

Abstract

Background/aims: 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-α, induced AP-2 expression in a time- and dose-dependent manner in cultured mesangial cells. PGE₂ and PGI₂ also induced AP-2 expression, while PGF_2α 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. Conclusion: 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.