Studies Of GR, HSP90 And Their Isoforms In PBMC And Neuropeptides In Plasma Of Patients With Systemic Lupus Erythematosus

Glucocorticoid ( GC) is the key factor of the hypothalamus - hypophysis -adrenal gland - immune axis. GC is a kind of steroid compound, synthesized and secreted by adrenal cortexzona fasiculata. Besides its very important regulation in some physiological processes including growth, auxesis, breeding and metabolism etc. , GC also has powerful and wide immunosuppressive function. GC not only takes part in regulating the immune homeostasis and inhibiting the over - activity of immune system, but also plays a very important role in the therapy of autoimmune diseases. Whereas, more and more evidence showed that GC - resistance was found in some tissues or organs under certain conditions, manifested different therapeutic responses in patients in clinic.GC takes effect by binding with the glucocorticoid receptor (GR) which generally residenting in the cytoplasm. There are two kinds of isoforms of GR as GRa under normal state and GRβ of variation fragment. Classical hormone effect is produced after the activation of GRa, but GRβ is unable to bind with hormone and only acts as an antagonist. GRa and heat shock protein 90 ( HSP90) binding into a maguns complex in cytoplasm under the situation of absence of ligand in order to prevent the action of GRa on DNA. The structure of the complex changes after binding with hormone. HSP90 detaches from GRa, followed by translocation of steroid - receptor complex and entering the nucleus. The effects of GC carries out through steroid - receptor complex binding with the specific DNA site ( hormone response fragment) in nucleus, switches on gene transcription and synthesizes various kinds of proteins. However, GRβ the vari-ation fragment takes effect as a endogenous inhibitory factor of GRa. Recent study shows that HSP90 participates in the binding of GC - GR and the activity of GR. HSP90 is one of the principal members of HSP superfamily, has two kinds of isoforms as HSP90ct and HSP90p, which have different functions. GR binds with the two HSP90 when no GC is active and forms HSP90 - GR complex which existing in the cytoplasm. When GC diffuses into cytoplasm, then binds with GR and cause the dissociation of HSP90 - GR complex, GR forms into di-mer after activating and binds GR response component in nucleus so that regulating the expression of proteins by adjusting and preventing the transcription of target gene. Thus HSP90 plays a key role in the formation and activation of GR. The change of HSP90 may lead to the change of activity in GR. A positive - regulation occurs when HSP90 ratio to GR appropriately, whereas negative - regulation occurs whether the ratio too high or too low. The expression of HSP90 increases under inflammation and correlated to the intensity of inflammation. With the aggravation of inflammation and the elongation of the last time, the expression of HSP90 increased. The increased expression of HSP90 may cause right shift of the response curve of GR binding with GC. Then the stability of GC -GR complex reduces and the effective number of GC decreases. So the change of HSP90 may serve as an additional marker of the effect of GC activity.Systemic lupus erythematosus (SLE) is a classic autoimmune disease and has unclear cause. Studies showed that the onset of SLE was a result of comprehensive effects of multi - factors. As the first selecting medicine in SLE treatment , GC takes an important part in life saving and life quality rising. However, the responses to GC are definitely different even in the same disease in clinic. Some patients have better therapeutic responses to GC, some worse even resistance. GC performed its biological effects mediated by GR and the intensity of biological effect parallels with the level of GR. The relationship between the number of GR and the effect of GC has been confirmed in many diseases. Recent studies observed that GR had internal correlation with human diseases, especially in immune diseases. It has been noticed that the disorder of GR might be related to immune diseases and many efforts has been done. But majority...