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

Mol Cell Endocrinol. 2009 Nov 13;311(1-2):24-31. doi: 10.1016/j.mce.2009.06.013. Epub 2009 Jul 5.

Abstract

In human kidneys, the mechanisms underlying angiotensinogen (AGT) 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 AGT mRNA (11+/-1%) and protein (7.0+/-0.9%) expression, high IL-6 receptor (IL-6R) expression (282+/-17%), and low basal NF-kappaB (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 30min) 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiotensin II / pharmacology
  • Angiotensinogen / genetics
  • Angiotensinogen / metabolism*
  • Antibodies / pharmacology
  • Cells, Cultured
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-1beta / pharmacology
  • Interleukin-6 / pharmacology*
  • Kidney Tubules, Proximal / cytology*
  • NF-kappa B / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-6 / metabolism
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / metabolism
  • Time Factors
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Antibodies
  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Interleukin-6
  • STAT3 Transcription Factor
  • Tumor Necrosis Factor-alpha
  • Angiotensinogen
  • Angiotensin II