The innate immune system and its complex interplay with the adaptive immune system are increasingly being recognized as important factors in the pathogenesis of chronic rhinosinusitis (CRS). Adaptive immune components, including resident and inflammatory cells, and their associated mediators, have been the subject of most research in CRS. For this reason, theories of CRS pathogenesis have involved the concept that inflammation, rather than infection, is the dominant etiologic factor in CRS. Therefore, glucocorticoids are increasingly used to treat CRS. This review will outline our current knowledge of action mode of glucocorticoids in CRS.
Cytokines ; Glucocorticoids ; Immune System ; Inflammation ; Receptors, Glucocorticoid

BACKGROUND AND OBJECTIVES: Glucocorticoids have demonstrated excellent efficacy in decreasing airway inflammation and controlling bronchial asthma symptoms. However, exacerbations of asthma are frequently observed even during treatment with inhaled glucocorticoids, and most of these episodes occur following viral upper respiratory infections (URI). Recently, it has been suggested that transient resistance to glucocorticoid developed after URI and this resistance to glucocorticoid in asthmatics was related to the increased expression of glucocorticoid receptor beta (GCRbeta). The aim of this study is to evaluate the expression of GCRbeta in asthmatics experiencing exacerbation after an episode of URI. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from asthmatics experiencing exacerbation after URI (n=15), stable asthmatics (n=23), and normal controls (n= 12). Exacerbated asthmatics were started on systemic glucocorticoids upto two weeks and PBMCs were obtained again after the treatment. The degree of expression of GCRbeta mRNA and ratio of GCRbeta/GCRalpha mRNA were calculated using the semi-quantitative RT-PCR. RESULTS: Compared with stable asthmatics and normal control, exacerbated asthmatics showed significantly higher expression of GCRbeta mRNA and ratio of GCRbeta/GCRalpha mRNA. However, comparing exacerbated asthmatics before and after treatment, we found no significant difference but trends of reduction in expression of GCRbeta mRNA and ratio of GCRbeta/GCRalpha mRNA after treatment. CONCLUSION: These findings suggest that transient resistance to corticosteroid in asthmatics experiencing exacerbation after an episode of URI may be related to increased expression of GCRbeta.
Asthma ; Glucocorticoids ; Inflammation ; Receptors, Glucocorticoid* ; Respiratory Tract Infections ; RNA, Messenger

BACKGROUND: Glucocorticoids (GC) are the most potent medications used to control airway inflammation associated with asthma. The aim of this study was to see whether alterations in GC receptor binding contribute to poor response to GC therapy in severe asthma. METHODS: Seventeen patients with severe persistent bronchial asthma were studied. Patients were classified as GC sensitive if their morning FEV1 increased >15% after a 1-week course of systemic GC (>prednisolone 40mg/day) and GC-resistant if they failed to increase >15%. GC receptor binding affinity for dexamethasone of peripheral blood mononuclear cells (PBMCs) were determined by using a radioligand binding assay and Scatchard analysis. RESULTS: There were no significant differences of age, serum IgE levels, peripheral blood eosinophils and atopic states between GC-resistant (n=10) and GC-responsive (n=7) groups. GC-resistant patients had significantly decreased GC receptor binding affinity (Kd=24.3+/-9.55) compared to the GC sensitive patients (Kd=13.5+/-1.48) and normal controls (n=6, Kd=4.24+/-1.09). CONCLUSION: These data suggest that decreased binding affinity of GC receptor is an important factor in clinical GC resistance in chronic severe asthma.
Asthma* ; Dexamethasone ; Eosinophils ; Glucocorticoids ; Humans ; Immunoglobulin E ; Inflammation ; Receptors, Glucocorticoid*

OBJECTIVETo investigate the distribution and pharmacokinetics of dexamethasone of different concentrations in the inner ears of SD rats after intratympanic injection.

METHODSTotally 144 adult SD rats were anaesthetized and dexamethasone sodium phosphate of different concentrations (5 mg/ml, 10 mg/ml, 20 mg/ml) was injected into the tympanums. The rats were sacrificed at various postinjection survival times (5 min, 10 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h, 48 h, 72 h), and every 4 rats were included into each group. Then after a series of processes the inner ear tissue was cryostat sectioned. The distribution of dexamethasone was evaluated using immunofluorescence with semiquantitative analysis. Immunofluorescence was also used in another 4 normal SD rats to detect the distribution of Glucocorticoid receptor (GR) in the inner ear.

RESULTSDexamethasone was observed initially 15 min after local drug administration and 30 min to its peak level. The highest concentration of dexamethasone labeling was seen in the spiral ligament, organ of Corti and spiral ganglion, which paralleled the distribution of GR. The tissue concentration of 10 mg/ml and 20 mg/ml groups was higher than 5 mg/ml every corresponding time point, and the lasting time was also prolonged from 48 hours to 72 hours.

CONCLUSIONSDexamethasone can enter into the cochlear tissue quickly after transtympanic injection, and its distribution accords nearly exactly with that of GR. Increase of the concentration of dexamethasone results in higher tissue distribution and longer lasting time.

Animals ; Cochlea ; metabolism ; Dexamethasone ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid ; metabolism

PURPOSE: To evaluate whether mucin gene expression is regulated by glucocorticoid hormone in cultured human corneal epithelial cells (HCECs). The effects of dexamethasone on the expression of MUC1 and MUC4, two known mucins produced by corneal epithelial cells, were determined. METHODS: HCECs were cultured in medium supplemented with dexamethasone. The modulations of MUC1 and MUC4 expression by dexamethasone were investigated by RT-PCR and Western blot analysis. RESULTS: The expression of MUC1 mRNA and its protein were enhanced in HCECs by dexamethasone. However, the treatment of HCECs with dexamethasone caused a decrease in MUC4 mRNA and its protein. These effects of dexamethasone on the MUC1 and MUC4 were abolished by a glucocorticoid antagonist (RU486). CONCLUSIONS: This study shows that dexamethasone is implicated in the expression of mucin in HCECs, and suggests that glucocorticoid receptor participates in the modulation of mucin production.
Blotting, Western ; Dexamethasone* ; Epithelial Cells* ; Epithelium, Corneal ; Gene Expression ; Humans* ; Mucins* ; Receptors, Glucocorticoid ; RNA, Messenger

BACKGROUND: Steroid-dependency is one of Phenotypes of severe asthma. Because steroid-dependent asthmatics require long-term systemic steroids to control their symptoms. they have potentially increased risks to experience serious events caused by systemic steroids. But the pathophysiology of steroid-dependent asthma is poorly understood. Differences of glucocorticoid and beta2-aderenergic receptor expression may have some roles in the pathophysiology of steroid-dependent asthma. OBJECTIVE: The aim of this study was to evaluate the differences of mRNA expression of glucocorticoid receptor and beta2-adrenergic receptor between the steroid-dependent severe asthmatics and those with mild-to-moderate severity. METHODS: Thirty-nine asthmatic patients were enrolled, twenty with mild-to-moderate severity and nineteen with steroid-dependent severe asthma. Induced sputum was collected using 4% hypertonic saline nebulization and total RNA was extracted from the cells collected. Using RT-PCR, we asessed the amounts of glucocorticoid receptor and beta2-adrenergic receptor mRNA semiquantitatively from the extracted RNA. RESULTS: There were no significant differences in sex, age, smoking history, duration of asthma, positive rate of atopy, and percent predicted value of FEV1 between the two groups. The amount of glucocorticoid receptor mRNA expression was significantly lower in steroid-dependent asthmatic group than in mild-to-moderate severity group(p<0.05). There was no significant difference in amount of beta2-adrenoreceptor mRNA expression between the two groups. CONCLUSION: Decreased expression of glucocorticoid receptor mRNA may have some role in the pathophysiology of steroid-dependent asthma.
Asthma* ; Humans ; Phenotype ; Receptors, Glucocorticoid ; RNA ; RNA, Messenger* ; Smoke ; Smoking ; Sputum ; Steroids

OBJECTIVETo investigate the effect of atopy on the expression of glucocorticoid receptors in children with bronchiolitis.

METHODSELISA was used to measure the changes in the serum levels of glucocorticoid receptor α (GRα) and glucocorticoid receptor β (GRβ) in the bronchiolitis group (77 children, including 34 children with atopy) and pneumonia group (68 children). Thirty-eight children who were prepared to undergo surgeries for non-infectious diseases and had no atopy or family history of allergic diseases were enrolled as the control group.

RESULTSThe bronchiolitis group and the pneumonia group had significant increases in the serum levels of GRα and GRβ compared with the control group (P<0.01), and the bronchiolitis group had significant increases in these levels compared with the pneumonia group (P<0.01). Compared with the control group and the pneumonia group, the bronchiolitis group had a significant increase in the GRα/GRβ ratio (P<0.01). Compared with the control group, the children with or without atopy in the bronchiolitis group had significant increases in the serum levels of GRα and GRβ (P<0.01). The non-atopic children in the bronchiolitis group had a significant increase in the serum level of GRβ compared with the atopic children (P<0.01). The atopic children in the bronchiolitis group had a significant increase in the GRα/GRβ ratio compared with the control group and non-atopic children in the bronchiolitis group (P<0.01).

CONCLUSIONSChildren with bronchiolitis have increased serum levels of GRα and GRβ. The children with atopy have an increased GRα/GRβ ratio, suggesting that the atopic children with bronchiolitis are highly sensitive to glucocorticoids.

Bronchiolitis ; blood ; Female ; Humans ; Hypersensitivity ; blood ; Infant ; Male ; Receptors, Glucocorticoid ; blood

Coronary Disease ; drug therapy ; metabolism ; Female ; Humans ; Male ; Receptors, Glucocorticoid ; metabolism

Glucocorticoid (GC) is currently the most effective drug for controlling persistent asthma; however, there is a significant difference in the response to GC among patients with asthma. Steroid-resistant asthma is one of the subtypes of asthma and has poor response to high-dose GC treatment. It may affect the quality of life of patients and even threaten their lives. Therefore, it is of great significance to explore the pathogenesis of steroid-resistant asthma and related targeted treatment strategy. In recent years, a variety of pathogeneses have been found to participate in the development and progression of steroid-resistant asthma, including the reduction in the binding between GC receptor and GC, the increase in the expression of GC receptor β, over-activation of nuclear transcription factor activating protein 1 and nuclear factor-κB, abnormality in histone acetylation, and immune-mediated cytokine dysregulation. In addition, many studies have shown that vitamin D can improve the sensitivity to GC among patients with steroid-resistant asthma. This article reviews the pathogenesis of steroid-resistant asthma and the influence of vitamin D.
Asthma ; Drug Resistance ; Glucocorticoids ; Humans ; Quality of Life ; Receptors, Glucocorticoid ; Vitamin D

Na+ homeostasis in the inner ear is important to maintain normal hearing and balance. Na+ transport in the inner ear is reported to be occurred in non-sensory epithelium of inner ear which forms a barrier between endolymphatic space and perilymphatic space. Functionally identified and constitutively active Na+ absorption sites in the inner ear are Reissner's membrane, outer sulcus cells, vestibular transitional cells, saccular nonsensory epithelial cells, and endolymphatic sac epithelial cells. Na+ transport in these epithelial cells is mediated by apically located epithelial Na+ channels (ENaC), nonselective cation channels and basolaterally located Na+, K+-ATPase. Na+ absorption is increased by glucocorticoid through glucocorticoid receptor or ATP through purinergic receptors depending on cell types.
Absorption ; Adenosine Triphosphate ; Ear, Inner ; Endolymphatic Sac ; Epithelial Cells ; Epithelium ; Hearing ; Homeostasis ; Membranes ; Receptors, Glucocorticoid ; Receptors, Purinergic ; Sodium