The Function Variety Of The Peripheral Blood Mononuclear Cells And The Expression Of Glucocorticoid Receptor Subunit In The Patients With Bronchial Asthma

Introduction Allergic asthma is a kind of chrinic airway inflammation characterized by many inflammation cells and cytokines included in the pathogenesis, which Th2 lymphocyte cytokines play an important role. Major advances have occurred in the past decade to more fully established the immunologic characteristics of the peripheral blood mononuclear cells (PBMCs) in asthma. The helper TO lymphocytes was induced by the dendritic cell's presented antigen and other cytokines, and the result is more Th2 lymphocytes were expressed ,meanwhile Th1 cells gone down. Afterwards, the bronchial hyperresponsiveness (BHR) and wheezing was caused by the overexpression of Th2 cytokines via IgE, eosinophil, and mast cells. The process that cytokines play a role in asthma pathogenesis is so complicated that so much investigation highlighted various results. Glucocorticoid have proved to be most effectivein modifying airway inflammation. The last few years have seen a growing understanding of the mechanisms of glucocorticoid action and, in particular, the receptor that mediates glucocorticoid actions, the glucocorticoid receptor. Glucocorticoid plays its anti-inflammation action in two ways, by combining with glucocorticoid receptor and binding to the targeted DNA sequence, glucocorticoid response elements; and by the interaction with other transcription factor. There are two subunit of GR, named GRα and GRβ. GRα is responsible for the induction and repression of target genes. GRβ has been found to act as a dominant negative inhibitor of GRα-mediated transactivation in in vitro studies with transfected cells. Studies done on patients with steroid-insensitive asthma demonstrated an overexpression ofGRp.Objective In the present study, we aimed to investigate the role of cytokines: tumor necrosis factor-cu interleukin-2s interferon-a, and their interaction in the peripheral blood mononuclear cells of patients with bronchial asthma, and its links with the expression of glucocorticoid receptor subunit and the therapeutical effect of glucocorticoid.Methods The diagnosis of asthma for these patiernts was set up on the standard provided by CMA 2002. PBMCs were obtained from all the subjects, including 12 asthmatic patients and 12 normal controls. The cells were cultured with 5%CO2, 37°C for 24 n 48 hours with or without interventions, such as : TNF-cu IL-2n IFN-a and DXM. The expression of glucocorticoid receptor subunit in PBMCs and the level of IL-6 from the supernatants were measured by means of immunocytochemistry and radioimmunoassay.Results The higher concentrations of IL-6 in the plasm from the asthmaticpatients as compared with normal subjects was measured in the present study(PO.01) . Incubation with single cytokine:TNF-ou IL-2N IFN-a or TNF-a+IL-2, or without stimulation induced significantly higher concentrations of IL-6 by PBMCs from the asthmatic patients as compared with normal subjects (P<0.0l) . There is no statistics significance of the level of IL-6 between the asthmatic patients and normal controls in IFN-0.05) . With the extend of culture time, more IL-6 were detected in the asthmatic patients cultured for 48hr than for 24hr in the group of stimulated by TNF-as IL-2s IFN-a v TNF-a+IL-2 (P<0.05). But we could not find such diffence about culture time in the group of IFN-a+IL-2s IFN-a+TNF-a and all the group cultured with DXM...