Advantages of Promoting Interleukin-10 by Silence of Histone Deacetylase 11 in Inducing Tolerance in Orthotopic Liver Transplantation in Rats

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.