ABSTRACT
AIMS: The aims of this study were to study the role of histone deacetylase 11 (HDAC11) in tolerance induction in orthotopic liver transplantation (OLT) in rats and to assess the advantages of gene therapy over the immunosuppressant FK506. METHODS: Recipients were assigned to an acute rejection group (AcR; group I), an FK506 intervention group (group II), and a tolerance group (group III). Acute rejection (AcR) was graded by the Banff scheme and we examined postoperative survival. The messenger RNA (mRNA) and protein expressions of histone deacetylase 11 (HDAC11) and interleukin (IL) 10 in liver tissue were detected using real-time polymerase chain reaction (PCR) and Western blots, respectively. Plasma levels of tumor necrosis factor (TNF)-α, IL-2, and IL-10 were measured using enzyme-linked immunosorbent Assays. RESULTS: Group I displayed severe, Group II had less, and Group III had no evidence of AR. The survivals among Group III were longer than those in Group I and Group II. IL-10 expression was promoted by HDAC11-shRNA at 7 days after OLT. Serum IL-2 and TNF-α levels were significantly lower among Group III compared with Groups I and II, whereas IL-10 showed the opposite result. CONCLUSIONS: Silence of HDAC11 promotes IL-10 expression and leads to tolerance following OLT in rats. Thus HDAC11 is a promising target for gene therapy to induce tolerance with advantages over immunosuppressive drugs.
Subject(s)
Gene Silencing , Histone Deacetylases/physiology , Immune Tolerance , Interleukin-10/physiology , Liver Transplantation , Animals , Base Sequence , Blotting, Western , Cytokines/blood , DNA Primers , Enzyme-Linked Immunosorbent Assay , Histone Deacetylases/genetics , Histone Deacetylases/metabolism , Interleukin-10/genetics , Interleukin-10/metabolism , RNA, Messenger/genetics , Rats , Real-Time Polymerase Chain ReactionSubject(s)
Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/virology , Hepatitis B Virus, Woodchuck/genetics , Hepatitis B/genetics , Animals , Cloning, Molecular , DNA, Complementary , Databases, Nucleic Acid , Gene Expression Regulation, Neoplastic , Gene Expression Regulation, Viral , Humans , Mice , Polymerase Chain ReactionABSTRACT
Electron transfer from the triplet excited state of thymine or thymidine to the disulphide compound lipoic acid (RSSR) was studied using KrF laser flash photolysis (248 nm, 20 ns). The electron transfer reaction rate constants, measured at 310 nm, were determined to be 1.3 x 10(10) M-1 s-1 and 6.9 x 10(9) M-1 s-1 for thymine and thymidine respectively. The transient absorbance at 400 nm in the presence of the quencher is attributed to the anion radical of lipoic acid.
Subject(s)
Electron Transport , Thioctic Acid/chemistry , Thymidine/chemistry , Thymine/chemistry , Lasers , Models, Chemical , Oxidation-Reduction , Photolysis , Spectrophotometry , Thymidine/radiation effects , Thymine/radiation effects , Ultraviolet RaysABSTRACT
A comparative study on HBV status and ets-2, IGF-II, C-myc and N-ras expression in 12 pairs of human primary hepatocellular carcinoma (PHC) and adjacent non-tumorous tissues (NT) showed that integrated forms of HBV DNA were present in 91.5% PHC and 75% NT. No specific integration sites were detected. Three PHC and 4 NT were found to have free forms of HBV DNA, which were defective in 2 PHC and 3 NT, i. e., being able to replicate but not to be secreted into the blood. At least one of four oncogenes studied was overexpressed in the 12 pairs of samples. IGF-II was expressed as 5.0 and 2.0 Kb fetal transcripts in 3 pairs of samples and 1 NT. Six NT had more than one of the four oncogenes that was expressed higher than PHC. This was commonly encountered in tissues with free forms of HBV DNA. The relation between HBV status, expression of ets-2, IGF-II, C-myc and N-ras and carcinogenesis of PHC is discussed.