BACKGROUND: Restrictions on graft size are a serious obstacle to the expansion of indications for adult recipients in living donor liver transplantation. Hepatocyte growth factor (HGF) has a crucial role in regeneration following hepatic injury. Rat cytokine-induced neutrophil chemoattractant (CINC), a member of the interleukin-8 superfamily in humans, has been implicated in chronic liver diseases or development of liver ischemia-reperfusion injury. Studies were performed to examine whether HGF influences the induction of CINC in hepatocytes. METHODS: Primary cultures of rat hepatocytes were treated with or without recombinant human (rh) HGF. The release of CINC into the culture medium and levels of CINC mRNA were measured using an enzyme-linked immunosorbent assay and Northern blot analysis. Transcription of nuclear factor (NF)-kappa B was detected by electrophoretic mobility shift assays. RESULTS: rhHGF increased the release of CINC in the medium dose- and time-dependently, showing a maximal effect at 100 ng/mL. Genistein (100 mumol/L) blocked the release of CINC stimulated by rhHGF. Levels of CINC mRNA were also increased, reaching a maximum at 8 hours after addition of rhHGF. Electrophoretic mobility shift assays revealed rhHGF activated transcription factor, NF-kappa B. CONCLUSION: These results suggest that HGF stimulates the induction of CINC gene expression through activation of NF-kappa B. CINC may be involved in the function of HGF during liver regeneration.
BACKGROUND: Restrictions on graft size are a serious obstacle to the expansion of indications for adult recipients in living donor liver transplantation. Hepatocyte growth factor (HGF) has a crucial role in regeneration following hepatic injury. Rat cytokine-induced neutrophil chemoattractant (CINC), a member of the interleukin-8 superfamily in humans, has been implicated in chronic liver diseases or development of liver ischemia-reperfusion injury. Studies were performed to examine whether HGF influences the induction of CINC in hepatocytes. METHODS: Primary cultures of rat hepatocytes were treated with or without recombinant human (rh) HGF. The release of CINC into the culture medium and levels of CINC mRNA were measured using an enzyme-linked immunosorbent assay and Northern blot analysis. Transcription of nuclear factor (NF)-kappa B was detected by electrophoretic mobility shift assays. RESULTS: rhHGF increased the release of CINC in the medium dose- and time-dependently, showing a maximal effect at 100 ng/mL. Genistein (100 mumol/L) blocked the release of CINC stimulated by rhHGF. Levels of CINC mRNA were also increased, reaching a maximum at 8 hours after addition of rhHGF. Electrophoretic mobility shift assays revealed rhHGF activated transcription factor, NF-kappa B. CONCLUSION: These results suggest that HGF stimulates the induction of CINC gene expression through activation of NF-kappa B. CINC may be involved in the function of HGF during liver regeneration.
Authors: Jillian Grygas; Nicole Steiger; Carrie L LeSeur; Benjamin L Unger; Dennis W McGee Journal: In Vitro Cell Dev Biol Anim Date: 2007-04-27 Impact factor: 2.416