IL-6 augments angiotensinogen in primary cultured renal proximal tubular cells

In human kidneys, the mechanisms underlying angiotensinogen (ACT) augmentation by interleukin 6 (IL-6) are poorly understood and the only information available is in HK-2, immortalized human renal proximal tubular epithelial cells. Therefore, the present study was performed to elucidate the effects of IL-6 on AGT expression in primary cultured human renal proximal tubular epithelial cells (RPTEC) after characterization of HK-2 and RPTEC. RPTEC showed low basal ACT mRNA (11 +/- 1%) and protein (7.0 +/- 0.9%) expression, high IL-6 receptor (IL-6R) expression (282 +/- 17%), and low basal NF-kappa B (43 +/- 7%) and STAT3 (43 +/- 7%) activities compared to those in HK-2. In RPTEC, AGT mRNA and protein expressions were enhanced by IL-6 (172 +/- 31% and 378 +/- 39%, respectively). This AGT augmentation was attenuated by an IL-6R antibody. STAT3 phosphorylation (366 +/- 55% at 30 min) and translocation were enhanced by IL-6. The AGT augmentation was attenuated by a STAT3 inhibitor. These data indicate that IL-6 increases AGT expression via STAT3 pathway in RPTEC. (C) 2009 Elsevier Ireland Ltd. All rights reserved.