title: Differential effects of insulin and dexamethasone on pulmonary surfactant-associated genes and proteins in A549 and H441 cells and lung tissue.
abstract: In this study, the effects of insulin and dexamethasone on the expression and mRNA transcription of 4 pulmonary surfactant-associated proteins [surfactant protein (SFTP)A, SFTPB, SFTPC and SFTPD] were examined. The commercially available cell lines, A549 and H441, were used as acceptable models of lung surfactant-producing cells. Subsequently, the effects of insulin on the expression of surfactant-associated proteins were examined in patients with lung adenocarcinoma during lung resection. Our results demonstrated the inhibitory effects of insulin on the transcription of the SFTPB, SFTPC and SFTPD genes in H441 cells and the SFTPB gene in A549 cells. Treatment with insulin significantly decreased the protein expression of SFTPA1 and SFTPA2 in the H441 cells and that of proSFTPB in the A549 cells. Dexamethasone promoted the transcription of the SFTPB, SFTPC and SFTPD genes in the A549 and H441 cells and reduced the transcription of the SFTPA1 and SFTPA2 genes in the H441 cells (SFTPA mRNA expression was not detected in A549 cells). Furthermore, we demonstrated that the mRNA levels of the selected genes were significantly lower in the cell lines compared to the lung tissue. A549 and H441 cells represent similar cell types. Yet, in our experiments, these cells reacted differently to insulin and/or dexamethasone treatment, and the mRNA levels of their main protein products, surfactant-associated proteins, were significantly lower than those in real tissue. Therefore, the results obtained in this study challenge the suitability of A549 and H441 cells as models of type II pneumocytes and Clara cells, respectively. However, we successfully demonstrate the possibility of studying the effects of insulin on pulmonary surfactant-associated genes and proteins in patients with lung adenocarcinoma.
authors.affiliation: Centre for Biomedical Image Analysis, Faculty of Informatics, Masaryk University, 60200 Brno, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Rucka
authors.forename: Petr
authors.initials: P
authors.lastname: Vanhara
authors.forename: Irena
authors.initials: I
authors.lastname: Koutna
authors.forename: Lenka
authors.initials: L
authors.lastname: Tesarova
authors.forename: Michaela
authors.initials: M
authors.lastname: Potesilova
authors.forename: Stanislav
authors.initials: S
authors.lastname: Stejskal
authors.forename: Pavel
authors.initials: P
authors.lastname: Simara
authors.forename: Jan
authors.initials: J
authors.lastname: Dolezel
authors.forename: Vaclav
authors.initials: V
authors.lastname: Zvonicek
authors.forename: Oldrich
authors.initials: O
authors.lastname: Coufal
authors.forename: Ivan
authors.initials: I
authors.lastname: Capov
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics / Q000378:metabolism; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000378:metabolism; D037661:Pulmonary Surfactant-Associated Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D007328:Insulin; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D003907:Dexamethasone