TY - JOUR
T1 - Regulation of expression of human SP-A1 and SP-A2 genes in fetal lung explant culture
AU - Karinch M, Anne
AU - Deiter, Gina
AU - Ballard, Philip L.
AU - Floros, Joanna
N1 - Funding Information:
The authors thank Susan DiAngelo, John Wert, John Gonzales, and Dr. Padma Kala for their contributions. This work was supported by grants HL49823 and HL19737 from the National Institutes of Health.
PY - 1998/6/16
Y1 - 1998/6/16
N2 - 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 γ (IFNγ), cyclic 3',5'adenosine monophosphate (cAMP), and tumor necrosis factor α (TNFα). 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) IFNγ 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 IFNγ 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.
AB - 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 γ (IFNγ), cyclic 3',5'adenosine monophosphate (cAMP), and tumor necrosis factor α (TNFα). 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) IFNγ 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 IFNγ 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.
UR - http://www.scopus.com/inward/record.url?scp=0032537455&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032537455&partnerID=8YFLogxK
U2 - 10.1016/S0167-4781(98)00047-5
DO - 10.1016/S0167-4781(98)00047-5
M3 - Article
C2 - 9689918
AN - SCOPUS:0032537455
SN - 0167-4781
VL - 1398
SP - 192
EP - 202
JO - Biochimica et Biophysica Acta - Gene Structure and Expression
JF - Biochimica et Biophysica Acta - Gene Structure and Expression
IS - 2
ER -