Abstract 291A Poster Session I, Saturday, 5/1 (poster 145A)

Insulin, at concentrations as low as 25 ng/ml, has been shown to decrease levels of mRNA for the surfactant proteins SP-A and SP-B in H441 cells, a human pulmonary adenocarcinoma cell line. Insulin-like growth factors (IGF-I and IGF-II) are polypeptides that are structurally homologous to proinsulin. The IGF-I receptor binds insulin, although with 1000-fold less affinity than IGF-I. To examine the hypothesis that the inhibitory effects of insulin on surfactant proteins are mediated via IGF receptors, we examined the effects of IGF-I and IGF-II on SP-A and SP-B gene expression in the H441 cell line. If insulin inhibits gene expression via binding to IGF receptors, one would predict that IGFs, even at low concentrations, would also inhibit surfactant protein gene expression. H441 cells were maintained in serum-free RPMI 1640 medium for 24 hours and then exposed to serum-free medium containing either no additions (control) or varying concentrations of IGF-I or IGF-II (1, 10 or 100 ng/ml) for 24 hours. SP-A and SP-B mRNA levels were analyzed by northern blot analysis in five experiments. The mRNA levels were corrected for loading and normalized to the control condition, which was made equal to one. (Table) Neither IGF-I nor IGF-II, at any concentration tested, had an effect on the levels of SP-A mRNA when compared to controls (ANOVA). These data are suggestive that insulin does not inhibit SP-A gene expression via binding to IGF receptors. In contrast, IGF-I significantly reduced SP-B mRNA levels, by ∼70% at 100 ng/ml, relative to controls (ANOVA, p<0.05). IGF-II also significantly inhibited SP-B mRNA levels, decreasing them by ∼50% at 100 ng/ml, relative to controls (ANOVA, p<0.05). These findings indicate that IGF-I and IGF-II may regulate SP-B gene expression.

Table 1 No caption available

(Supported by NIH-HL 50050)