title: Influence of glucocorticoids, neuregulin-1β, and sex on surfactant phospholipid secretion from type II cells.
abstract: Glucocorticoids induce lung fibroblasts to produce fibroblast-pneumocyte factor, a peptide that stimulates type II cells to synthesize pulmonary surfactant. This effect is known to be more apparent in cells derived from female fetuses, a characteristic that has been attributed to sex-linked differences in the fibroblasts. In the current study, it has been shown that dexamethasone enhances both β-adrenergic receptor (β-AR) activity (1.3- to 1.6-fold increase) and (-)-isoproterenol-induced secretion of surfactant (1.8- to 1.9-fold increase) in type II cells. However, fibroblast-conditioned media (FCM), prepared in the presence of dexamethasone, generates a much greater response to (-)-isoproterenol (3.1- to 3.8-fold increase). Furthermore, each of these effects is more pronounced if both cell types are female-derived. It is hypothesized that the enhanced response to glucocorticoids is the result of a synergistic effect between the steroid and a component of FCM. Neuregulin-1β (NRG1β), which is elevated in FCM generated in the presence of dexamethasone, influences not only the rate of surfactant secretion and the β-AR activity in type II cells, but also enhances in both sexes the cellular response to (-)-isoproterenol. These results suggest that NRG1β might be more effective than glucocorticoids in treating prematurely born male infants, which are known to respond poorly to glucocorticoids. Given that glucocorticoids are known to induce higher levels of β-AR mRNA, the effect of NRG1β, alone and in combination with dexamethasone, on β-AR gene expression was measured using qRT-PCR. Whereas NRG1β had no effect alone, in combination with dexamethasone it produced up to a 4.2-fold elevation in the level of β-AR mRNA.
authors: School of Veterinary and Life Sciences, Murdoch Univ., Murdoch, WA 6150, Australia. G.Maker@murdoch.edu.au.
authors: George
authors: G
authors: King
authors: Jolanta E
authors: JE
authors: Damas
authors: Max H
authors: MH
authors: Cake
authors: David
authors: D
authors: Berryman
authors: Garth L
authors: GL
authors: Maker
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects*; D000818:Animals; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D020890:Neuregulin-1 / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis / Q000187:drug effects; D012737:Sex Factors
chemical_list: D017077:Culture Media, Conditioned; D005938:Glucocorticoids; D020890:Neuregulin-1; D010743:Phospholipids; D011663:Pulmonary Surfactants; D011943:Receptors, Adrenergic, beta; C117467:neuregulin beta; D003907:Dexamethasone; D007545:Isoproterenol
keywords: (-)-isoproterenol; dexamethasone; type II pneumocytes; β-adrenergic receptor gene expression; β-adrenergic receptors