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Am J Physiol Heart Circ Physiol 274: H331-H341, 1998;
0363-6135/98 $5.00
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Vol. 274, Issue 1, H331-H341, January 1998

IL-1beta alters the expression of the receptor tyrosine kinase gene r-EphA3 in neonatal rat cardiomyocytes

Yun You Li, Charles F. McTiernan, and Arthur M. Feldman

Cardiovascular Research Laboratories, Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213

To identify proinflammatory cytokine responsive genes in the myocardium, we used differential display to study RNA isolated from neonatal rat cardiac myocytes treated with tumor necrosis factor-alpha (TNF-alpha ) and interleukin-1beta (IL-1beta ). Sequence analysis of differential display products confirmed by reverse Northern blots revealed one clone as the partial sequence of an Eph-related receptor tyrosine kinase (r-EphA3). In cardiac myocytes, 36-h exposure to TNF-alpha and IL-1beta reduced r-EphA3 transcripts to 59.9% (P < 0.01) of control levels; this effect was largely dependent on IL-1beta . Western blot analysis showed that changes in r-EphA3 protein levels reflect that seen for transcripts. Cardiac nonmyocytes expressed substantially lower levels of r-EphA3. Full-length r-EphA3 cDNA clone (3,077 base pair) yielded an amino acid sequence with 90-98% homology to the Eph receptor human EphA3, chick EphA3, and mouse EphA3. In the adult rat, r-EphA3 transcripts were most abundant in the heart, brain, and lung. These results suggest that IL-1beta may exert its effect on cardiac myocytes at least in part by altering r-EphA3 expression.

proinflammatory cytokine; differential display; cardiac myocytes


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