Regulation of surfactant protein D in human fetal lung.
Surfactant protein D (SP-D) is a collagenous glycoprotein, produced by lung type II cells, that has structural and functional similarities with SP-A. In this study we postulated that SP-D and SP-A gene expression are regulated in a similar fashion to provide a coordinated local immune defense response to pulmonary infection. We determined content of SP-D protein and mRNA in second-trimester fetal lung and in postnatal tissue by protein blotting and hybridization analyses. Low levels of SP-D mRNA and protein were detected at 16 wk gestation, before appearance of SP-A, and levels increased during gestation. The content of SP-D did not change during 5 days of explant culture, whereas SP-A increased manyfold. Dexamethasone treatment during culture increased SP-D mRNA and protein about 2-fold with maximal response after 1 to 3 days' exposure to 100 nM steroid; under the same conditions SP-A mRNA content is inhibited. There was no significant change in SP-D mRNA after treatment of explants with adenosine 3',5'-monophosphate (cAMP) analog or interferon-gamma, agents which increase SP-A gene expression, nor after exposure to phorbol ester, tumor necrosis factor-alpha, or lipopolysaccharide at concentrations that reduced levels of SP-A mRNA by approximately 50%. We conclude that SP-D in the human lung is under developmental and glucocorticoid regulation occurring at a pretranslational level. SP-D is not influenced by inflammatory mediators that regulate SP-A, suggesting that these two proteins are not coordinately regulated in response to lung infection.
Dulkerian
S J
SJ
Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, USA.
Gonzales
L W
LW
Ning
Y
Y
Ballard
P L
PL
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D046508:Culture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005865:Gestational Age; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008168:Lung / Q000196:embryology* / Q000378:metabolism*; D011510:Proteolipids / Q000235:genetics / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D006023:Glycoproteins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003907:Dexamethasone; D007371:Interferon-gamma