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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Yang, Zhen Zhu, Ping Guo, Chunming Sun, Kang Zhu, Xiaoou |
| Description | Author Affiliation: Yang Z ( School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, P.R. China.) |
| Abstract | CONTEXT: Glucocorticoids are crucial in fetal lung function. The amount of cortisol available to its receptors is increased by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). Glucocorticoids and IL-1beta are known to induce 11beta-HSD1 expression in a number of tissues, but controversial results were obtained with regard to 11beta-HSD1 expression in human fetal lung. OBJECTIVE: We examined the expression of 11beta-HSD1 and its regulation by cortisol and IL-1beta in human fetal lung. RESULTS: Immunohistochemistry revealed 11beta-HSD1 expression in the epithelium and mesenchymal layer of the small bronchus and bronchiole of human fetal lung at 8 months but not at 4 months gestation, which was confirmed by PCR revealing 11beta-HSD1 mRNA expression in the fetal lung tissue. By using a cell line derived from human fetal lung fibroblasts, we demonstrated that cortisol (10(-5) to 10(-3) mmol/liter) or IL-1beta (0.1 to 10 ng/ml) induced 11beta-HSD1 mRNA expression in a concentration-dependent manner. The induction of 11beta-HSD1 by IL-1beta was further increased by cortisol, whereas the induction of cyclooxygenase 2 by IL-1beta was inhibited by cortisol. Nuclear factor kappaB activation inhibitor could only block the induction of cyclooxygenase 2 but not 11beta-HSD1 by IL-1beta, suggesting that different mechanisms were utilized by IL-1beta in the regulation of 11beta-HSD1 versus proinflammatory mediators. Global inhibition of CCAAT-enhancer-binding proteins (C/EBPs) with transfection of C/EBP-specific dominant-negative expression plasmid could attenuate the induction of 11beta-HSD1 by IL-1beta, suggesting that C/EBPs may mediate the induction of 11beta-HSD1 by IL-1beta. CONCLUSIONS: 11beta-HSD1 is expressed in human fetal lung; cortisol and IL-1beta could synergistically induce its expression. |
| ISSN | 0021972X |
| e-ISSN | 19457197 |
| Journal | The Journal of Clinical Endocrinology & Metabolism |
| Issue Number | 1 |
| Volume Number | 94 |
| Language | English |
| Publisher | Oxford University Press |
| Publisher Date | 2009-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | 11-beta-hydroxysteroid Dehydrogenase Type 1 Genetics Fetus Enzymology Gene Expression Regulation, Developmental Drug Effects Hydrocortisone Pharmacology Interleukin-1beta Lung Ccaat-enhancer-binding Protein-alpha Physiology Cyclooxygenase 2 Immunohistochemistry Research Support, Non-u.s. Gov't Discipline Endocrinology Discipline Metabolism |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry (medical) Endocrinology, Diabetes and Metabolism Clinical Biochemistry Biochemistry Endocrinology |
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