ErbB receptor regulation by dexamethasone in mouse type II epithelial cells.
Glucocorticoids stimulate foetal surfactant synthesis. Therefore, they are used in impending pre-term birth. One mechanism of action on surfactant synthesis is through the induction of neuregulin (NRG) secretion by foetal lung fibroblasts. The direct effects on signalling pathways, and specifically on erbB receptors in foetal type II cell surfactant synthesis, are less well understood. The present authors studied the effect of known promoters of foetal surfactant synthesis (namely dexamethasone and mature (i.e. NRG-containing) fibroblast-conditioned medium (FCM)) on erbB receptor activation, protein content and dimerisation patterns in foetal mouse lung type II cells. Dexamethasone inhibited surfactant synthesis in immature type II cells at day (d)16 of gestation, while the mature FCM had stimulatory effects. Both treatments directly stimulated surfactant synthesis in more mature (d17) cells. At this gestational day, dexamethasone had only a small effect on phosphorylation, but it stimulated the protein levels of all four erbB receptors. Dexamethasone effects were distinct from those of mature FCM, which stimulated both protein content and phosphorylation of all erbB receptors and of the signalling intermediate phospholipase Cgamma. Dexamethasone modulated erbB receptor dimerisation patterns, such that erbB2 became the main dimerisation partner for erbB4. In conclusion, dexamethasone signalling involves erbB receptors in foetal type II cells, in a manner similar to, but distinct from, neuregulin-containing fibroblast-conditioned medium signalling.
Dammann
C E L
CE
Division of Newborn Medicine, Tufts University and Floating Hospital for Children, Boston, MA, USA. dammann.christiane@mh-hannover.de
Nassimi
N
N
Liu
W
W
Nielsen
H C
HC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D019281:Dimerization; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D047468:Immunoprecipitation; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D020880:Neuregulins / Q000494:pharmacology; D010766:Phosphorylation; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D066247:Receptor, ErbB-4; D015398:Signal Transduction
D000893:Anti-Inflammatory Agents; D017077:Culture Media, Conditioned; D003907:Dexamethasone; D066246:ErbB Receptors; D020880:Neuregulins; D011663:Pulmonary Surfactants; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; C587690:Erbb4 protein, mouse