Regulation of expression of human SP-A1 and SP-A2 genes in fetal lung explant culture

Anne Karinch M, Gina Deiter, Philip L. Ballard, Joanna Floros

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47 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)192-202
Number of pages11
JournalBiochimica et Biophysica Acta - Gene Structure and Expression
Volume1398
Issue number2
DOIs
StatePublished - Jun 16 1998

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Genetics

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