Differential effects of glucocorticoid on expression of surfactant proteins in a human lung adenocarcinoma cell line

Michael A. O'Reilly, Adi F. Gazdar, Randal E. Morris, Jeffrey A. Whitsett

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Synthesis of pulmonary surfactant-associated glycoproteins of Mr 28 000-36 000 (SP-A) and Mr 42 000-46 000 (proSP-B) has been identified in a continuous cell line derived from a human lung adenocarcinoma. SP-A was detected by immunoblot analysis, ELISA assay and by [35S]methionine labelling of the cells. SP-A was secreted into the media as an endoglycosidase F sensitive glycoprotein which co-migrated with the isoforms of SP-A identified in human lavage fluid by 2D-IEF-SDS-PAGE. Hybridization of cellular RNA with SP-A-specific cDNA identified an abundant 2.2 kb mRNA species, identical to that observed in human lung. SP-A RNA and protein content were markely inhibited by dexamethasone in a dose-dependent fashion. Under identical culture conditions, synthesis of a distinct surfactant protein, SP-B, was markedly stimulated by the glucocorticoid. The SP-B precursor was secreted into the media as heterogenous Mr 42 000-46 00 protein, pI 4.6-5.1, and was sensitive to endoglycosidase F. Synthesis of proSP-B was enhanced by the glucocorticoid in a dose-dependent fashion and was associated with increased SP-B mRNA of 2.0 kb detected by Northern blot analysis. The cell line secreted proSP-B as Mr 42 000-46 000 glycosylated protein and did not process the precursor to the Mr 7000-8000 and secretes peptide. In summary, a human adenocarcinoma cell line has been identified which synthesized and secretes two surfactant-associated proteins, SP-A and proSP-B. Glucocorticoid enhanced SP-B but inhibited SP-A expression in this cell line. The identification of a continuous cell line secreting surfactant proteins may be useful in the study of synthesis and secretion of these important proteins and for production of the proteins for clinical uses.

Original languageEnglish (US)
Pages (from-to)194-204
Number of pages11
JournalBBA - Molecular Cell Research
Volume970
Issue number2
DOIs
StatePublished - Jun 30 1988

Keywords

  • (Human lung)
  • Corticosteroid
  • Gene expression
  • Pulmonary surfactant

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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