Recombinant interleukin-1 beta inhibits elastin formation by a neonatal rat lung fibroblast subtype.
The effect of recombinant interleukin-1 beta (rIL-1 beta) on elastin accumulation by lipid-laden interstitial cells (LIC) derived from neonatal rat lung was examined. The LIC, a fibroblast subtype, synthesized large amounts of elastin which was deposited into the extracellular matrix. This elastin was alkali-resistant and had an amino acid composition typical of adult rat elastin. Treatment of lipid-laden interstitial cell cultures with rIL-1 beta at 100 pg/ml caused a dramatic decrease in elastin accumulation as assessed by hot alkali treatment and transmission electron micrographs of the cell cultures. Tropoelastin formation was selectively decreased by rIL-1 beta relative to other proteins. Steady state levels of elastin mRNA were slightly decreased by rIL-1 beta at 5 pg/ml and markedly decreased by rIL-1 beta at 50 pg/ml or greater. The addition of indomethacin had no effect on rIL-1 beta-induced decreases in elastin mRNA levels. Inhibiting protein synthesis with cycloheximide blocked the effect of rIL-1 beta on elastin mRNA levels. The level of alpha 1(I) collagen mRNA was decreased by rIL-1 beta, but only at concentrations higher than that needed to induce a decrease in elastin mRNA. These data indicate that rIL-1 beta decreased steady state levels for elastin mRNA and elastin accumulation and can selectively regulate the accumulation of elastin and collagen.
Berk
J L
JL
Pulmonary Center, Boston University School of Medicine, Massachusetts.
Franzblau
C
C
Goldstein
R H
RH
D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D015152:Blotting, Northern; D003513:Cycloheximide / Q000494:pharmacology; D004549:Elastin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology
D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004549:Elastin; D003513:Cycloheximide; D007213:Indomethacin