The role of PPARγ expression in patients with aGVHD following allo-HSCT

Abstract

Objective To explore the role of peroxisome proliferator-activated receptor (PPAR)-gamma (γ) in acute graft versus host disease (aGVHD) after allogenic hematopoietic stem cell transplantation (allo-HSCT). Methods Sixty-five patients under allo-HSCT during 2013.06 to 2016.04 and 10 healthy controls were enrolled in this study. Peripheral blood (PB) of patients was collected at 15th, 30th, 60th, and 90th day after allo-HSCT and at the onset of aGVHD. The mRNA expression of PPARγ, IFNγ and T-bet was detected by the real-time PCR. Furthermore, we conducted mixed lymphocyte reaction (MLR) to detect the proliferation of active lymphocytes under different concentrations of PPARγ agonist rosiglizone. Results Among 65 patients after allo-HSCT, aGVHD occurred in 45 patients within 90 days. The expression of PPARγ mRNA in healthy controls was significantly lower than that in patients after allo-HSCT within 90 days (P<0.05). The expression of PPARγ mRNA hold steady in non-GVHD patients within 90 days after allo-HSCT, and was significantly lower in GVHD group than in non-GVHD group (P<0.05). The PPARγ expression in severe aGVHD (grade Ⅲ-Ⅳ) was lower than in mild aGVHD (grade Ⅰ-Ⅱ) patients (P<0.05). The expression of IFNγ and T-bet was increased in aGVHD patients and negatively correlated with PPARγ mRNA expression (P<0.05). The experiment of MLR revealed that PPARγ agonist rosiglitazone above 25 μmol/L could dose-dependently inhibit the proliferation of lymphocytes. Conclusion Low expression of PPARγ is associated with aGVHD occurrence and degree. PPARγ agonist can inhibit the proliferation of lymphocytes, which may be a new way to treat aGVHD. Key words: Peroxisome proliferator-activated receptor-gamma; Hematopoietic stem cell transplantation; Graft versus host disease; Interferon-gamma; T-bet transcription factor