Expression of 11beta-hydroxysteroid dehydrogenase type 1 in human fetal lung and regulation of its expression by interleukin-1beta and cortisol.
BACKGROUND
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.
School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, P.R. China.
Zhen
Z
Yang
Ping
P
Zhu
Chunming
C
Guo
Xiaoou
X
Zhu
Kang
K
Sun
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000032:analysis / Q000235:genetics*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000235:genetics; D005333:Fetus / Q000201:enzymology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000494:pharmacology*; D008168:Lung / Q000201:enzymology*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D053583:Interleukin-1beta; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D006854:Hydrocortisone