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

Glucocorticoid inhibition of human SP-A1 promoter activity in NCI-H441 cells

“…It is possible that sequence differences between the SP-A2 promoters from NCI-H441 cells and the genomic clone could account for this discrepancy. With regard to the inhibitory effect of dexamethasone, studies using fetal lung explants have shown that SP-A1 alleles are more responsive to dexamethasone [16], that the SP-A2 gene is more responsive [19], or that both SP-A genes are equally responsive to dexamethasone [18]. Thus apparent discrepancies among these studies may be a result of differential allelic regulation, with certain SP-A1 or SP-A2 alleles responding differently.…”

“…In human fetal lung explants, the synthetic glucocorticoid dexamethasone increases SP-A mRNA levels at low concentrations ( 10 nM), but decreases SP-A mRNA and protein levels at higher concentrations (100 nM) [10][11][12][13][14][15]. Moreover, the degree of inhibition of SP-A1 and SP-A2 expression varies in explant cultures [16][17][18][19]. In contrast to the biphasic effects seen in lung explant culture, dexamethasone has only an inhibitory effect on SP-A1 and SP-A2 expression in the lung adenocarcinoma cell line NCI-H441 ( [18,20,21] and R. R. Hoover, K. H. Thomas and J. Floros, unpublished work), which occurs partly at a transcriptional level.…”

Characterization of a human surfactant protein A1 (SP-A1) gene-specific antibody; SP-A1 content variation among individuals of varying age and pulmonary health

“…Although the ratio of SP-A1 to SP-A2 has been suggested to be 2:1 based on the 2:1 composition of the SP-A trimer (76), studies of mRNA content in surgical lung tissues and fetal lung explants (38,39) have shown that the gene-specific mRNA content varied from this proposed 2:1 ratio. This, assuming that SP-A mRNA levels reflect protein levels, raised the possibility that homooligomers of SP-A1 or SP-A2 do exist.…”

“…Biochemical differences in response to ozone exposure (36, 77, 81), oligomerization patterns (36, 77), aggregation (71), and the ability to bind carbohydrates (60) were also observed for SP-A1 and SP-A2 variants. Quantitative differences between SP-A1 and SP-A2 genes were observed in H441 cells, a lung adenocarcinoma cell line (46,70), and in fetal lung explant cultures under basal conditions and/or in response to dexamethasone (24,38,46,51,56). Quantitative differences in the total SP-A mRNA (18) or protein levels (25, 27) among individuals were also observed.…”

“…More than 30 alleles have been characterized for these two genes, with four SP-A1 alleles (6A, 6A 2 , 6A 3 , and 6A 4 ) and six SP-A2 alleles (1A, 1A 0 , 1A 1 , 1A 2 , 1A 3 , and 1A 5 ) most frequently observed in the general population (10,14,16,40,67). Although a high level of sequence similarity is shared among the SP-A genes and their corresponding alleles, in vitro studies have identified both qualitative (22,36,57,60,77,80,81) and quantitative (24,35,38,46,56,69,70,78,79) differences between the two genes.…”