Indirect inhibition of myocyte RNA and protein synthesis by interleukin-1.
Soluble mediators of the inflammatory response may directly influence myocardial function and metabolism in the absence of myocardial cell necrosis. Previous reported experimental data have demonstrated that the monokine interleukin-1 (IL-1) can produce myocardial depression and may influence muscle protein metabolism. To further investigate this hypothesis, IL-1 was added to neonatal rat cardiac muscle cell (MC) cultures with and without additional rat cardiac non-muscle cells (NMC). Incorporation of 3H-uridine or 14C-phenylalanine into acid-insoluble material was utilized as a measure of RNA or protein synthesis. IL-1 in concentrations of up to 500 units/ml had no effect on MC RNA or protein synthesis. When NMC were added to the MC culture, IL-1 exhibited a concentration-dependent inhibition of both RNA and protein synthesis, with effects apparent at concentrations as low as 5 units/ml. Supernatants from IL-1-treated NMC cultures exerted a dose dependent reduction on the incorporation of radiolabeled precursor into MC cultures, suggesting production of a soluble substance mediating the IL-1 effect. Supernatants from IL-1 treated rat skin fibroblasts or rat skeletal muscle myoblasts increased MC radiolabeled precursor incorporation slightly, in contrast to the decrease seen with NMC supernatant. Furthermore, IL-1 treated NMC supernatant had no inhibitory effect on skeletal myoblasts. We conclude that IL-1 decreases protein and RNA synthesis in MC cultures through a second mediator elaborated from the NMC population.
Hosenpud
J D
JD
Division of Cardiology, Oregon Health Sciences University, Portland 97201.
Campbell
S M
SM
Pan
G
G
D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D003864:Depression, Chemical; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology*; D009124:Muscle Proteins / Q000096:biosynthesis; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects*; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects*
D003470:Culture Media; D007375:Interleukin-1; D009124:Muscle Proteins; D012313:RNA