Expression Of PPARγ In Patients After Allo-HSCT Correlates With AGVHD

Objective:To explore the role ofPeroxisome proliferator-activated receptor(PPAR)-gamma(γ)in acute graft versus host disease(aGVHD)after allogenic hematopoietic stem cell transplantation(allo-HSCT).Methods:65 patients under allo-HSCT and 10 healthy controls were enrolled in study.Peripheral blood(PB)of patients was collected at 15 days,30 days,60 days,and 90 days after allo-HSCT.The mRNA expression of PPARγ,IFNγ,T-bet and other cytokines was detected by the real-time PCR.Lymphocytes were isolated from blood of 2 healthy controls,and then mixed lymphocyte reaction(MLR)was conducted to detect the proliferation of active lymphocytes under different concentration of PPAR γ agonist and soluble epoxide hydrolase(sEH)inhibitor which can elevate the content of PPARγ agonist.Results:Among 65 patients after HSCT,aGVHD occurred in 45 patients.Expression of PPARγ mRNA in healthy controls were significant lower than that in patients after allo-HSCT within 90 days(P<0.05).The expression of PPARγ mRNA in non-GVHD patients within 90 days after allo-HSCT had no significant difference(P>0.05),while was significantly lower in GVHD group than in non-GVHD group(P<0.05).PPARγ expression in severe aGVHD(grade Ⅲ to Ⅳ)was lower than mild aGVHD(grade Ⅰ to Ⅱ)patients(P<0.05).The expression of IFNγ and T-bet increased in aGVHD patients and were negatively correlated with PPARγ mRNA expression(P<0.05).PPARγ agonist rosiglitazone above concentration of 25μmol/L had dose-dependent inhibition effect on proliferation of lymphocytes(P<0.01).sEH inhibitor had no effect on the proliferation.Conclusion:Low expression of PPARγ is associated with aGVHD occurrence and degree,andnegatively related to the expression of Th1 associated cytokines.Overexpression of PPARγ can inhibit the proliferation of lymphocytes.