lnterleukin-1α Upregulates the Expression of Surfactant Protein-A in Rabbit Lung Explants

Abstract

Interleukin-1 (IL-1) is an important participant in infectious and inflammatory conditions. Interleukin-1 receptor antagonist (IL-1 ra) prevents the effect of IL-1. We have shown that injection of interleukin-1 α (IL-1α) into the amniotic fluid of pregnant rabbits stimulates the expression of surfactant protein-A (SP-A) in the lungs of the fetuses. We hypothesized that IL-1α similarly enhances the expression of SP-A in rabbit lung explants in vitro. Explants obtained from 22-day fetal rabbit lungs were cultured in Waymouth’s medium on a rotating platform in the presence or absence of IL-1α (5.7–570 ng/ml) or IL-Ira (1–10 μg/ml). Dibutyryl cAMP (1 mM) served as a positive control. After 3 days in culture, the explants were harvested and Northern analysis of SP-A was performed using the 1.9-kb rabbit SP-A cDNA probe. IL-1α and dibutyryl cAMP increased the expression of SP-A twofold, as judged by video densitometry. IL-1ra did not change SP-A expression as compared with controls, suggesting that endogenous IL-1 activity was not responsible for the basal level of SP-A expression in the explants. Dibutyryl cAMP increased the expression of SP-B mRNA, whereas IL-1 α had no effect on SP-B mRNA concentration. We conclude that inflammatory mediators interact with lung cells to alter synthesis of important components of the surfactant system.

Intraamniotic interleukin-1 accelerates surfactant protein synthesis in fetal rabbits and improves lung stability after premature birth.

“…In a preliminary study, lung explants, adsorbed to the culture dish, were cyclically exposed to air and the culture medium. Under these conditions, the increase in SP-A mRNA by dibutyryl cAMP was less than during the present culture system (34).…”

“…IL-1␣ also stimulated the expression of SP-A in fetal rabbit lung explants in culture, whereas under these conditions SP-B was unaffected. On the other hand, IL-1ra, which is present in high concentration in amniotic fluid (18), did not modify the expression of SP-A, -B, or -C mRNA when given in excess intraamniotically to fetal rabbits or added to fetal lung cultures (34). This suggests that endogenous IL-1 activity does not play a role in the expression of surfactant proteins in fetal lung during normal preterm gestation.…”

Intra-Amniotic Interleukin-1α Treatment Alters Postnatal Adaptation in Premature Lambs

“…TNF downregulates the expression of mRNA for surfactant pro teins A and B [25] and inhibits phosphatidyl choline synthesis in type II cells [26]. In con trast, IL-la upregulates surfactant protein A mRNA expression in fetal rabbit lung ex plants [27] and increased Sat PC pool sizes in the present preterm lamb study. There is no information available concerning functional effects of TNF on the developing lung.…”

The intrauterine expression of surfactant protein D in the terminal airways of human fetuses compared with surfactant protein A

“…None of the cases showing findings associated with preterm PROM or infection were included in this study since it is well known that the expression of SP-A and D is upregulated by inflammatory cytokines [1,3,8]. Thus, in this study, which was rather small, the natural course of the expression of SP-D was detected.…”