| ObjectivePolymyositis and dermatomyositis ( PM/DM) belong to idiopathic inflammatory myopathy, characterised by the weakness of proximal muscle and nonsup-purative inflammation of skeletal muscle. It is termed as dermatomyositis if myo-sitis accompanies polymorphous rash. The etiology and pathogenesis of PM/DM is still unclear. Recent studies indicate that PM is mainly the humoral immunity induced, while DM is mainly the cell immunity induced autoimmune disease. Glucocorticoid (GC) is the key molecular of hypothalamic - pituitary - adrenal axis ( HPA) , which is a kind of steroid compound, synthesized and secreted by adrenal cortexzona fasiculata. Besides its very important regulation action on some physiological processes ,such as growth, endorcrine and metabolism, GC has powerful immunosuppression function. At present, GC is still extensively used to treat many autoimmune diseases, including PM/DM. But different patients have different response to GC, about 1/5 to 1/3 PM/DM patients are un-sensitive, even resistant to GC therapy. The cases resistant to GC therapy challenge the clinical treatment. However, the molecular mechanism unsensitive to GC, even resistant to GC therapy, is not fully understood untill now.The important physiological and pharmacological action of GC is mediated by glucocorticoid receptor ( GR) existing in cytoplasma. GR binds with two HSP90 and HSP90 maintains GR in an inactive form in the absence of GC. Hormone binding to the ligand - binding domain of GR elicits a series of molecular events including dissociation from the HSP90 chaperone and changes of confor-mation of the receptor itself, allowing the activation or repression of target genes. So HSP90 plays an importamt role in maintaining the construction and function of GR. Optimal ratio of HSP90/GR is positive regulation,while abnormally high and low ratio of HSP90/GR was negative regulation. The distribution of HSP90 in tissue determines the specificity and sensitivity of GC, The higher expression of HSP90 mRNA, the more difficult for GC to inhibit lymphocytes proliferation. Moreover, expression of HSP90 increases in some pathological conditions, such as inflammation and autoimmune.Many studies indicate that the amount of GR parallels with the GC clinical efficacv. Moreover , the disorder of GC - GR are related with the onset of someautoimmune diseases. Alternative splicing involving exon 9 of the GR gene gives rise to two homologous messenger ribonucleic acids (mRNAs) and protein iso-forms, termed GRα and GR β. GRa is the classical ligand binding protein for GC, which mediates GC metabolic effects primarily by interaction of the GR with GC response element (GRE) in the promoters of GC responsive genes. On the other hand,GRβ is deficient in hormone binding. Some studies found high expression of GRβ mRNA in peripheral blood mononuclear cells ( PBMCs) of GC - resistant bronchial asthma, ulcerative colitis and so on, which suggests that GRβ may inhibit GRa action and lead to GC - resistant. But other studies challenge the concept of GRβ as a dominant negative inhibitor of GRa. Cell transfec-tion experiment showed that GRβ could inhibit the GRa action in a dose - dependent pattern, but only when GRβ exceeded GRa at least for 5 - fold to 10 -fold molar , could observe the inhibiting function of GRa. However, other study indicated that even GRβ exceeded GRa for 10 -fold molar, GRβ was still unable to inhibit GRa function. The role of GRβ during the GC resistance needs to be studied further.But some of the studies above only detected the GR amount of PBMCs using radioimmunoligand method, and did not distinguish the two different isoforms a and p. Moreover, HSP90, the important chaperone, was not investigated. Though other studies distinguished the two different isoforms a and β, the conclusions were contradictory,even opposite. At present, there is no related reportabout the relationship between the expressions of HSP90, GR, GRa and GRβ mRNA in PBMCs of PM/DM patients and the GC effic...
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