title: Interleukin-6 and rs1800796 locus single nucleotide polymorphisms in response to hypoxia/reoxygenation in hepatocytes.
abstract: Ischemia-reperfusion injury due to hypoxia/reoxygenation (H/R) is one of the main causes of liver damage during liver surgery. Donor interleukin-6 (IL-6) rs1800796 single nucleotide polymorphisms (SNPs) affect the metabolism of tacrolimus following liver transplantation-related hepatic H/R. This study investigated the response of IL-6 and its promoter polymorphisms to hepatic H/R in liver parenchymal cells. The association between IL-6 rs1800796 SNPs and IL‑6 expression was measured in 84 disease-free liver tissues using tissue microarrays and immunohistochemistry. Subsequently, LO2G, LO2C and NC-LO2 cells were successfully constructed via stable lentivirus-mediated transfection. The effects of IL-6 and its SNPs on the biological function of LO2 cells were examined using a cell model of H/R. Our results revealed that IL-6 was mainly expressed in hepatocytes. The intermediate IL-6 expression rate in genotype CC carriers was higher than that in genotype CG/GG carriers (P=0.006), which was subsequently verified at the IL-6 mRNA level (P=0.002). The concentrations of alanine aminotransferase in the LO2G cells were significantly higher than those in the LO2C cells following H/R for 6 h and H/R for 24 h (P<0.05). The viability of the LO2C cells was higher than that of the LO2G cells (P<0.05). Furthermore, the expression of IL-6 and its downstream molecules was significantly increased in the LO2C cells compared with the LO2G cells (P<0.05). Therefore, the sequence variants of rs1800796 SNPs (G→C) exhibit an increased IL-6 transcription efficiency in liver parenchymal cells. In addition, the increased expression of IL-6 protects the hepatocytes following hepatic H/R injury.
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Shaohan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Tonghai
authors.initials: T
authors.lastname: Xing
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
mesh_terms: D000328:Adult; D000483:Alleles; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D056426:Genetic Loci; D005822:Genetic Vectors / Q000378:metabolism; D005838:Genotype; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D016086:Lentivirus / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D010100:Oxygen