Regulation of expression of human SP-A1 and SP-A2 genes in fetal lung explant culture.
Human pulmonary surfactant protein A (SP-A) is genetically complex and its regulation may also be complex, reflecting genotypic variability. Fetal lung explants were used to study the regulation of the SP-A genes, SP-A1 and SP-A2, by dexamethasone, interferon, gamma (IFN gamma), cyclic 3',-5' adenosine monophosphate (cAMP), and tumor necrosis factor alpha (TNF alpha). For comparison, the mRNA levels of surfactant protein B (SP-B) and its response to test substances were also examined. Results showed: (a) In control culture total SP-A mRNA varied widely among explants (C.V. = 0.70) compared with SP-B (C.V. = 0.26) (b) IFN gamma significantly increased total SP-A mRNA but there were marked differences among fetal lungs in response to all treatments. (c) SP-A1 mRNA concentration is higher than SP-A2 in both control and treated explants. (d) SP-A1 alleles are inhibited to a greater degree by dexamethasone than SP-A2 alleles. The relative effect of cAMP and IFN gamma on SP-A1 and SP-A2 mRNA varied widely among explants. We conclude that SP-A genotype may account in part for the marked differences in SP-A mRNA concentration among fetal lungs and that the SP-A genes and/or alleles may be differentially regulated.
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey 17033, USA.
A M
AM
Karinch
G
G
Deiter
P L
PL
Ballard
J
J
Floros
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000483:Alleles; D017398:Alternative Splicing / Q000235:genetics; D000998:Antiviral Agents / Q000494:pharmacology; D046508:Culture Techniques; D000242:Cyclic AMP / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005333:Fetus; D015870:Gene Expression / Q000235:genetics; D005786:Gene Expression Regulation; D005796:Genes / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D005938:Glucocorticoids / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008168:Lung; D011510:Proteolipids / Q000235:genetics*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015203:Reproducibility of Results; D012107:Research Design; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000998:Antiviral Agents; D005938:Glucocorticoids; D006728:Hormones; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; C445842:SFTPA1 protein, human; C445843:SFTPA2 protein, human; D014409:Tumor Necrosis Factor-alpha; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003907:Dexamethasone; D007371:Interferon-gamma; D000242:Cyclic AMP