Interleukin-1 beta increased [3H]leucine incorporation by 30% and net cellular protein content by 20% in cultured neonatal rat cardiac myocytes, inducing hypertrophy without DNA synthesis.
IL-1 beta induces cardiac myocyte hypertrophy and alters gene expression toward a fetal phenotype while downregulating calcium regulatory genes via a nitric oxide-independent mechanism.
p-value: p=<0.001
Mononuclear cell infiltration and local cytokine elaboration are hallmarks of inflammatory and immunologic heart diseases. To test the hypothesis that cytokines can modulate cardiac myocyte growth and phenotype, myocytes cultured from neonatal rat hearts were exposed to IL-1 beta, an inflammatory cytokine prevalent in myocardial inflammation. IL-1 beta (2 ng/ml, 24 h) increased 3Hleucine incorporation by 30 +/- 4% (P 10-fold, n = 4), and decreased mRNA levels for sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) (-46 +/- 7%; P < 0.001; n = 11), calcium release channel (CRC) (-65 +/- 11%, P < 0.001, n = 8) and voltage-dependent calcium channel (VDCC) (-53 +/- 7%, P < 0.001, n = 8). NG-monomethyl-L-arginine (1 mM), an inhibitor of nitric oxide (NO) synthesis, did not inhibit the IL-1 beta-induced protein synthesis or changes in mRNA levels. In ventricular myocardium obtained from adult rats treated with lipopolysaccharide (4 mg/kg intraperitoneally 18 h) to stimulate systemic cytokine production, there were changes in the mRNA levels for beta-MHC (6 +/- 1-fold, P < 0.01, n = 4), SERCA2 (-65 +/- 4%, P < 0.0001, n = 4), CRC (-67 +/- 5%, P < 0.001, n = 4), and VDCC (-58 +/- 5%, P < 0.001; n = 4) that were qualitatively similar to those observed in cultured myocytes. Thus, IL-1 beta, acting via an NO-independent mechanism, caused myocyte hypertrophy associated with induction of fetal genes (ANF and beta-MHC) and downregulation of three important calcium regulatory genes (SERCA2, CRC, and VDCC). IL-1 beta may contribute to the abnormal structural and functional alterations of cardiac myocytes in conditions marked by mononuclear cell infiltration.
Thaik et al. (Tue,) conducted a other in Myocardial inflammation. Interleukin-1 beta (IL-1β) vs. Control was evaluated on [3H]leucine incorporation (p=<0.001). Interleukin-1 beta increased [3H]leucine incorporation by 30% and net cellular protein content by 20% in cultured neonatal rat cardiac myocytes, inducing hypertrophy without DNA synthesis.