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Am J Physiol Endocrinol Metab 278: E738-E743, 2000;
0193-1849/00 $5.00
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Vol. 278, Issue 4, E738-E743, April 2000

Thyroid hormone-induced stimulation of the sarcoplasmic reticulum Ca2+ ATPase gene is inhibited by LIF and IL-6

Bernd Gloss1, Sonia Villegas1, Francisco J. Villarreal, Anselmo Moriscot, and Wolfgang H. Dillmann

Department of Medicine, University of California San Diego, La Jolla, California 92093-0618

We investigated the effects of the leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) on 3,3', 5-triiodo-L-thyronine, or thyroid hormone (T3)-stimulated sarcoplasmic reticulum Ca2+ ATPase (SERCA2) gene expression on cultured neonatal rat cardiac myocytes. A reduction of T3 induced increases in SERCA2 mRNA levels after co-treatment with LIF or IL-6. To investigate for the molecular mechanism(s) responsible for the blunted gene expression, a 3.2-kb SERCA2 promoter construct containing a reporter gene was transfected into cardiac myocytes. T3 treatment stimulated transcriptional activity twofold, whereas co-treatment with T3 and either of the cytokines caused an inhibition of T3-induced SERCA2 transcriptional activity. A T3-responsive 0.6-kb SERCA2 construct also showed a similar inhibition by cytokines. Cytokine inhibition of SERCA2 transcriptional activity was also evident when a 0.6-kb SERCA2 mutant, T3-unresponsive promoter construct was used. Treatment with T3 and cytokines showed a significant decrease in transcription when a reporter construct was used that was comprised of direct repeats of SERCA2 thyroid response element I. These data provide evidence for cytokine-mediated inhibitory effects on the SERCA2 promoter that may be mediated by interfering with T3 action.

cardiac hypertrophy; heart failure; contraction; relaxation; cytokines


1 Bernd Gloss and Sonia Villegas made equal contributions to this study.




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