Effects Of Peroxisome Proliferator-activated Receptor-γagonist 15-deoxy-â–³^12,14-prostaglandin J₂ On The Survival And Apoptosis Of Thyrocytes

Objective: To investigate the expression of PPARγin thyrocytes after exposure of the thyroid stimulating antibody (TSAb) and the effects of peroxisome proliferator-activated receptor-γagonist 15-Deoxy-△12, 14-Prostaglandin J2 (15d-PGJ2) on the survial and apoptosis of thyrocytes stimulated by TSAb.Methods:In primary cultured human thyrocytes, the expression of PPARγmRNA and PPARγprotein were detected by real time-PCR and Western blot methods, effects of 15d-PGJ2 on different concentrations and at different action times on survial of thyrocytes were measured by MMT analysis,the morphological changes of apoptosis were determined by Hochest/PI double fluorescence staining,and the apoptosis rate of thyrocytes stimulated by 15d-PGJ2 on different concentrations at 24h action time was measured by flow cytometry. Meanwhile, we utilized PPARγantagonist GW9662 to block PPARγpath and then observed the effects of 15d-PGJ2 on thyrocytes stimulated by TSAb.Results: 1.The expression of PPARγmRNA and PPARγprotein were detected in thyrocytes of TSAb group,TSAb negative group and control group,but the ones in TSAb group were considerably lower than those in two other groups(P<0.05).2. 15d-PGJ2 could inhibit the survival of thyrocytes, which was dose and time-dependent.The peak was observed when stimulated by 20μmol/L 15d-PGJ2 for 24h.;5-40μmol/L 15d-PGJ2 could promote the apoptosis of thyrocytes stimulated by TSAb in dose-dependent(p<0.05);The apoptosis motivated by 20μmol/L 15d-PGJ2 could be partly reversed by 10μmol/L PPARγantagonist GW9662(p<0.05).Conclusions:1. The expression level of PPARγin thyrocytes stimulated by TSAb is considerably depressed. In GD,TSAb probably inhibitting PPARγfunction results in thyrocytes apoptosis obvious reduction.2.PPARγagonist 15d-PGJ2 has the effect of inhibition on the growth of thyrocytes stimulated by TSAb ,which is time and dose-dependent in a range.3. PPARγagonist 15d-PGJ2 could induce the apoptosis of thyrocytes stimulated by TSAb ,which participats in its inhibition effect on the growth of thyrocytes.4. The apoptosis motivating effects of PPARγagonist 15d-PGJ2 could be partly reversed by PPARγantagonist GW9662,which shows that it induces the apoptosis of thyrocytes stimulated by TSAb through PPARγpathway.The specific mechanism is not clear,which need further investigation.5. The elucidation of the molecular mechanism may develop new treatments for GD.