Injection of interleukin-1α (IL- 1α) into the amniotic fluid accelerates the maturation of the surfactant system, improves the lung stability after premature birth, and upregulates the expression of surfactant protein A (SP-A) and SP-B. According to preliminary study, IL-1α increases SP-A mRNA in explants of the immature lung (Pediatr Res 37:61A, 1995). The aim of the present study was to investigate the mechanism of the IL-1 induced increase in SP-A mRNA.
Lung explants from 22-day old fetal rabbits were cultured on a filter paper laying on a metallic grid in a culture dish. The tissue pieces were partly in contact with the atmosphere, partly in the Waymouth's medium in the presence or absence of recombinant human IL-1α (rh IL-1α, 57 or 570 ng/ml). At the end of incubation the RNA was isolated, and SP-A mRNA was quantitated by Northern analysis. The get loading artifacts were compensated by quantifying mRNA of cytochrome oxidase subunit II. Within two hours after the addition of 570 ng/ml of rh IL-1α SP-A mRNA increased 12.7 ± 1.3-fold compared to placebo-treated explants. The effect was dose dependent. After six hours, the effect of IL-1α decreased. SP-A mRNA increased in placebo-treated explants, and by 48 h the IL-1α induced increase in the expression of SP-A was 3.5 ± 0.6 fold. The inhibition of prostaglandin synthesis did not decrease the effect of IL-1. As studied using actinomycin D, IL-1α did not increase the stability of SP-A mRNA. Inhibitors of protein phosphorylation decreased the effect of IL-1 on the expression of SP-A mRNA. According to present results, IL-1 increases the transcription of SP-A mRNA in the immature lung. We propose IL-1 activates an as yet unidentified nuclear transcription factor.
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Cho, S., Nguyen, Q., Bry, K. et al. Study on the Mechanlsm of Interleukin-1 Induced Increase in Surfactant Protein A. † 237. Pediatr Res 41 (Suppl 4), 42 (1997). https://doi.org/10.1203/00006450-199704001-00257
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DOI: https://doi.org/10.1203/00006450-199704001-00257