title: Thermal injury-induced increases of hepatocyte SOCS3 lead to decreases in STAT3.
abstract: Previous work in this laboratory has shown an increase of both mRNA and protein for suppressor of cytokine signaling 3 (SOCS3) in rat liver after thermal injury. This study identifies which liver cell type (parenchymal or non-parenchymal) is responsible for the postburn increase in SOCS3 and how this increase is connected to the signal transducer and activator of transcription (STAT) pathway. Parenchymal (hepatocytes) and non-parenchymal cells were isolated by Liberase digestion from postburn day 1 (PBD1) rats (including sham controls) and were analyzed for the expression of SOCS3 mRNA and protein and STAT3 and p-STAT3 protein. Reverse transcriptase (RT)-PCR performed on the isolated cells showed a significant increase of SOCS3 in the hepatocytes, but not in the non-parenchymal cells. When isolated hepatocytes from rats and the human hepatocyte cell line, HepG2, were cultured in the presence of IL-6, both showed an increase in SOCS3 mRNA expression. Anti-SOCS3, anti-STAT3, and anti-phosphorylated STAT3 labeling in both postburn rat liver and isolated hepatocyte cells that were cultured in the presence of IL-6 revealed that an increase in SOCS3 protein was accompanied by decrease in STAT3 protein. We propose that thermal injury stimulates non-parenchymal cells to produce cytokines, including IL-6, which in tum stimulate the Jak/STAT pathway in hepatocytes. The signal transduction pathway triggered by non-parenchymal cells causes an increase in SOCS3 production, which in turn induces the reduction of STAT3 protein in the hepatocytes.
authors.affiliation: Department of Surgery, University of Cincinnati, Ohio 45229, USA.
authors.forename: Fansheng
authors.initials: F
authors.lastname: Kong
authors.forename: Xialing
authors.initials: X
authors.lastname: Guo
authors.forename: J Greg
authors.initials: JG
authors.lastname: Noel
authors.forename: Denise A
authors.initials: DA
authors.lastname: Wells
authors.forename: Glenda J
authors.initials: GJ
authors.lastname: Lovell
authors.forename: Cora K
authors.initials: CK
authors.lastname: Ogle
mesh_terms: D000818:Animals; D002056:Burns / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D011506:Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D015850:Interleukin-6; D011506:Proteins; D012097:Repressor Proteins; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C491410:Socs3 protein, rat; C494088:Stat3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors