Hypoxia Inducible Factor and Interleukin-6 mediated activation of human Angiotensinogen is not coupled in Huh7 cells

Alcohol usage is linked to increased blood pressure and fibrotic transformation of the liver after the hepatocyte death. Angiotensinogen (AGT) is the source of Ang II which is produced by sequential action of renin followed by angiotensin converting enzyme. The blood AGT levels correlate to blood pressure, therefore, an increase in blood AGT levels result into corresponding increase in Ang II levels affecting blood pressure regulation and liver fibrogenic processes. Alcohol metabolism by the liver produces oxidative stress (ROS) activating hypoxia inducible transcription factor-1alpha (HIF-1α). Chronic alcoholics possess increased levels of interleukin-6 with circulating ethanol in blood. The effects of HIF-1α and STAT3 activation mediated effects on AGT secretion by Huh7 cells were studied by treatment with hypoxia mimetics and IL-6 with ethanol to determine the combined effects at 24 and 48 hrs. post treatments. AGT secretion levels which were increased with Huh7 hepatocytes after deferoxamine (60 nM and 120 nM) treatments post four- and six-hours treatments were not sustained post 24 and 48 hrs. The IL-6 (10 ng/ml) mediated AGT secretion was sustained till 24 and 48 hrs. Treatment with 50 mM ethanol did not affect HIF-1α mediated effect on AGT secretion while slightly increasing secretion with IL-6. HIF-1α and IL-6 combined treatment did not produce additive effects on secretion of AGT at 24 or 48 hrs. Treatment of ethanol with HIF-1α activation and IL-6 did not increase AGT secretion. It is concluded that HIF-1α activation effects on AGT secretion may be for shorter time period.