Clinical Significance And Changes Of Glucocorticoid Receptor And Heat Shock Protein 90α,β In Masthenia Gravis Patients Treated With Glucocorticoid

Objective: Myasthenia gravis (MG) is a kind of autoimmune disease (AID) which is treated mainly by Glucocorticoid (GC). Many studies suggest that the effect of GC on autoimmune disease be related to glucocorticoid receptor (GR) and heat shock protein 90 (HSP90) which is an important chaperonin of GR. In order to further explore the means of exogenous GC how to play its pharmacologic effects and interaction among GC, GR and HSP90, the expression of GRα,GRβ,HSP90α,HSP90βin children with MG pre or post GC treatment were investigated.Methods: The clinical data of children with MG were summarized. GRα,βmRNA expression in peripheral blood mononuclear cells (PBMCs) were detected by RT-PCR and their protein expression were determined by immunocytochemical method (ICC). The serum cortisol was detected by chemoluminescence.Results: 1.The serum cortisol of children with MG pre-GC treatment was significantly higher than children with MG post-GC treatment and normal control(P<0.05). There was no difference between children with MG post-GC treatment and normal control(P>0.05).2. Both mRNA expression and protein expression of GRα,βand hsp90α,βin PBMC of either patients pre-GC treatment or post-GC treatment were significantly higher than normal control(P<0.05). However, the expression of PBMC HSP90βin PBMC of patients post-GC treatment was higher than that of patients pre-GC treatment(P<0.05).3. A little of GRα,βwas expressed in cytoplasma and cell nucleus of PBMC in normal control, however they were identified to mainly express in cytoplasma and cell nucleus of PBMC of patients pre-GC treatment,but mainly expressed in cell nucleus and cytoplasma of PBMC of patients post-GC treatment. A little of HSP90α,βwas expressed in cell nucleus of PBMC in normal control, however they were identified to mainly express in cytoplasma and cell nucleus of PBMC of patients pre-GC treatment, but mainly expressed in cell nucleus of PBMC of patients post-GC treatment.4.The positive correlation was found between GRβand HSP90βexpression in PBMC of patients and normal control. Moreover, the expression of HSP90αin PBMC was positively correlated with HSP90βexpression between MG patients pre-GC treatment and post-GC treatment(P<0.05).Conclusion: 1.The significant change of serum cortisol between MG patients and normal control indicated that it is possible that existing abnormal conveying and utilization of GC in MG patients;2. There was significant difference in the expression level and distribution of GRα, GRβ, HSP90α, HSP90βin PBMC between MG patients and normal control. Enhancement of the combination of HSP90βto GRα, which inhibited the combination of GRαand GC, and then HSP90βcut down the combination, conveying and utilization of GC.3. Although there were no significant changes in expression level of GRα, GRβ, HSP90αand HSP90βin PBMC, the change of the expression distribution might induce the combination of GC and GRβdecreased,and the ability of HSP90βcombination and conveying of GC enhanced, which leaded to serum cortisol obviously decreased,and clinical symptom of MG patients were improved.