The Effect of Nitric Oxide on Ammonia Decomposition in Co-cultures of Hepatocytes and Hepatic Stellate Cells

Abstract

Hepatic functions, such as albumin secretion and ammonia metabolism, are upregulated in response to hepatocyte growth factor (HGF) produced by hepatic stellate cells (HSC), as well as nitric oxide (NO) produced by endothelial cells under shear stress. However, the simultaneous effect of HSC and NO has not been previously investigated in a tri-co-culture model containing hepatocytes with HSC and endothelial cells under shear stress. We hypothesized that NO inhibits HGF production from HSC. To test this idea, we constructed a mono-culture model of hepatocytes and a co-culture model of hepatocytes and HSC and measured ammonia decomposition and HGF production in each model under NO load. Ammonia decomposition was significantly higher in the co-culture model under 0 ppm NO load, but no significant increase was observed under NO load. In the co-culture model, HGF was produced at 1.0 ng/mL under 0 ppm NO load and 0.3 ng/mL under NO load. Ammonia decomposition was increased by 1.0 ng/mL HGF, but not by 0.3 ng/mL HGF. These results indicated that NO inhibits HGF production from HSC; consequently, the effects of NO and co-culture with HSC cannot improve hepatic function simultaneously. Instead, the simultaneous effect of 1.0 ng/mL HGF and NO may further enhance hepatic function in vitro.

Maxillary Sinus Wall Thickening in Silent Sinus Syndrome

“…[1,2,15] H. pylori in the sinus would remain surrounded with ammonia at its immediate vicinity, the local irritation caused by this ammonia stimulates mucus secretion; therefore, existence of H. pylori in the maxillary sinus will cause continued mucus production either directly or via the effect of shear stress until obliteration or collapse of the sinus cavity happens in silence. [25][26][27] For the same reason that H. pylori is essentially a natural bacterium and non-pathogenic in nature, the mucus produced in the sinus is not infected, hence; it is odorless and is not associated with fever or other constitutional symptoms of maxillary sinusitis such as pain, a matter that explains the silent consequences of the sinus syndrome. Usually obstruction favors infection, hence; what causes absence of infection in an obstructed maxillary sinus unless the causative reason is not essentially an infective pathogen.…”

Impaired integrin α5/β1‐mediated hepatocyte growth factor release by stellate cells of the aged liver

“…HSC fulfill important functions as mesenchymal stem cells during liver homeostasis and regeneration (Kordes, Sawitza, Götze, Schumacher, & Häussinger, 2015). One function is the release of trophic factors such as hepatocyte growth factor (HGF) which maintains hepatocyte functions and induces their proliferation after liver injury to facilitate tissue repair (Stolz, Mars, Petersen, Kim, & Michalopoulos, 1999; Sumii et al, 2016).…”