Interleukin-1 alpha upregulates the expression of surfactant protein-A in rabbit lung explants.
Interleukin-1 (IL-1) is an important participant in infectious and inflammatory conditions. Interleukin-1 receptor antagonist (IL-1ra) prevents the effect of IL-1. We have shown that injection of interleukin-1 alpha (IL-1 alpha) 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-1 alpha 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-1 alpha (5.7-570 ng/ml) or IL-1ra (1-10 micrograms/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-1 alpha 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 alpha 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.
Dhar
V
V
Department of Pediatrics, University of California, Irvine, USA.
Hallman
M
M
Lappalainen
U
U
Bry
K
K
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism*; D009924:Organ Culture Techniques; D011247:Pregnancy; D011510:Proteolipids / Q000235:genetics*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits
D007375:Interleukin-1; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D003994:Bucladesine