Effect of glucocorticoids on C3 gene expression by the A549 human pulmonary epithelial cell line

Terence L. Zach, Laura Diane Bilek, Vicki A. Herrman, M. Patricia Leuschen, Margaret K. Hostetter

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The third component of C, C3, is the key opsonin of the C cascade and is produced locally within the lung by pulmonary epithelial cells, macrophages, and fibroblasts. Because glucocorticoids regulate the maturation and expression of several physiologically important genes in pulmonary epithelial cells, we examined the effects of glucocorticoids on C3 mRNA expression and C3 synthesis by the human pulmonary epithelial cell line, A549. Treatment with dexamethasone enhanced C3 production in a time- and dose-dependent fashion such that concentrations of dexamethasone ≥ 0.001 μM significantly increased C3 production on day 3 of culture. Natural glucocorticoids, corticosterone, cortisol, and 11-deoxycortisol also increased C3 concentrations in A549 supernatants. Both cycloheximide and the glucocorticoid receptor antagonist, RU486, individually inhibited the effect of dexamethasone on C3 production. Northern analysis demonstrated that the steady state 5.2-kb C3 message increased in A549 cells within 10 h of treatment with dexameth-asone. RU486 inhibited the effect of dexamethasone on C3 mRNA expression. The integrity of the C3 thiolester bond, as measured by [3H]iodoacetic acid titration and hemolytic assay, was not disrupted by dexamethasone. We conclude that glucocorticoids such as dexamethasone enhance the expression of C3 mRNA and increase the production of functionally active C3 by A549 cells by a mechanism that is mediated by the intracellular glucocorticoid receptor.

Original languageEnglish (US)
Pages (from-to)3964-3969
Number of pages6
JournalJournal of Immunology
Volume148
Issue number12
StatePublished - Jun 15 1992

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Dexamethasone
Glucocorticoids
Epithelial Cells
Gene Expression
Cell Line
Lung
Glucocorticoid Receptors
Messenger RNA
Complement Hemolytic Activity Assay
Cortodoxone
Iodoacetic Acid
Opsonin Proteins
Cycloheximide
Corticosterone
Hydrocortisone
Fibroblasts
Macrophages
Genes
A549 Cells

ASJC Scopus subject areas

  • Immunology

Cite this

Zach, T. L., Bilek, L. D., Herrman, V. A., Leuschen, M. P., & Hostetter, M. K. (1992). Effect of glucocorticoids on C3 gene expression by the A549 human pulmonary epithelial cell line. Journal of Immunology, 148(12), 3964-3969.

Effect of glucocorticoids on C3 gene expression by the A549 human pulmonary epithelial cell line. / Zach, Terence L.; Bilek, Laura Diane; Herrman, Vicki A.; Leuschen, M. Patricia; Hostetter, Margaret K.

In: Journal of Immunology, Vol. 148, No. 12, 15.06.1992, p. 3964-3969.

Research output: Contribution to journalArticle

Zach, TL, Bilek, LD, Herrman, VA, Leuschen, MP & Hostetter, MK 1992, 'Effect of glucocorticoids on C3 gene expression by the A549 human pulmonary epithelial cell line', Journal of Immunology, vol. 148, no. 12, pp. 3964-3969.
Zach, Terence L. ; Bilek, Laura Diane ; Herrman, Vicki A. ; Leuschen, M. Patricia ; Hostetter, Margaret K. / Effect of glucocorticoids on C3 gene expression by the A549 human pulmonary epithelial cell line. In: Journal of Immunology. 1992 ; Vol. 148, No. 12. pp. 3964-3969.
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