Glucocorticoid receptor localization in normal and asthmatic lung

被引:134
作者
Adcock, IM
Gilbey, T
Gelder, CM
Chung, KF
Barnes, PJ
机构
[1] Thoracic Medicine, National Heart and Lung Institute, Imp. Coll. Sci., Technol. and Med., London
[2] Thoracic Medicine, National Heart and Lung Institute, Imp. Coll. Sci., Technol. and Med., London SW3 6LY, Dovehouse Street
关键词
D O I
10.1164/ajrccm.154.3.8810618
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
The localization and distribution of the human glucocorticoid receptor (CR) mRNA and protein was investigated in human lung obtained from transplant donors and recipients by in situ hybridization, RNA blot analysis, immunolocalization, and Western analysis. Subjects were either nonasthmatic or had mild asthma requiring only beta(2)-agonists. No difference in amount of CR mRNA was found in total RNA isolated from nonasthmatic or asthmatic donor lung. In situ hybridization showed the highest concentration of GR mRNA in the alveolar walls and vascular endothelium and smooth muscle, with lesser amounts in the airway epithelium and smooth muscle. There was no change in the level or sites of expression of CR mRNA between normal and asthmatic subjects. Immunolocalization of GR confirmed the in situ hybridization data. There was no change in the level or sites of expression of GR, in either the lung or airway, between normal and asthmatic subjects, Immunolocalization of GR in bronchial biopsies from two normal and asthmatic subjects confirmed the localization and distribution of GR. Western analysis and mobility shift assays confirmed no differences in GR levels between the two subject groups. The localization of CR mRNA and protein to specific cell types within lung and airway will make it possible to study the cellular targets of glucocorticoid therapy in inflammatory lung diseases such as asthma.
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收藏
页码:771 / 782
页数:12
相关论文
共 43 条
[1]   THE EFFECTS OF GLUCOCORTICOIDS ON PHORBOL ESTER AND CYTOKINE-STIMULATED TRANSCRIPTION FACTOR ACTIVATION IN HUMAN LUNG [J].
ADCOCK, IM ;
SHIRASAKI, H ;
GELDER, CM ;
PETERS, MJ ;
BROWN, CR ;
BARNES, PJ .
LIFE SCIENCES, 1994, 55 (14) :1147-1153
[2]   INCREASED TACHYKININ RECEPTOR GENE-EXPRESSION IN ASTHMATIC LUNG AND ITS MODULATION BY STEROIDS [J].
ADCOCK, IM ;
PETERS, M ;
GELDER, C ;
SHIRASAKI, H ;
BROWN, CR ;
BARNES, PJ .
JOURNAL OF MOLECULAR ENDOCRINOLOGY, 1993, 11 (01) :1-7
[3]  
ADCOCK IM, 1995, J IMMUNOL, V154, P3500
[4]  
ADCOCK IM, 1995, AM J PHYSIOL, V268, pC338
[5]   CYTOKINES - COORDINATORS OF IMMUNE AND INFLAMMATORY RESPONSES [J].
ARAI, K ;
LEE, F ;
MIYAJIMA, A ;
MIYATAKE, S ;
ARAI, N ;
YOKOTA, T .
ANNUAL REVIEW OF BIOCHEMISTRY, 1990, 59 :783-836
[6]   IMMUNOSUPPRESSION BY GLUCOCORTICOIDS - INHIBITION OF NF-KAPPA-B ACTIVITY THROUGH INDUCTION OF I-KAPPA-B SYNTHESIS [J].
AUPHAN, N ;
DIDONATO, JA ;
ROSETTE, C ;
HELMBERG, A ;
KARIN, M .
SCIENCE, 1995, 270 (5234) :286-290
[7]   DRUG-THERAPY - INHALED GLUCOCORTICOIDS FOR ASTHMA [J].
BARNES, PJ .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (13) :868-875
[8]  
BOGGARAM V, 1989, J BIOL CHEM, V264, P11421
[9]   AUTOREGULATION OF GLUCOCORTICOID RECEPTOR GENE-EXPRESSION [J].
BURNSTEIN, KL ;
BELLINGHAM, DL ;
JEWELL, CM ;
POWELLOLIVER, FE ;
CIDLOWSKI, JA .
STEROIDS, 1991, 56 (02) :52-58
[10]   HORMONAL-REGULATION OF PEPTIDE RECEPTORS AND TARGET-CELL RESPONSES [J].
CATT, KJ ;
HARWOOD, JP ;
AGUILERA, G ;
DUFAU, ML .
NATURE, 1979, 280 (5718) :109-116