Attenuation of NF-κB signalling in rat cardiomyocytes at birth restricts the induction of inflammatory genes

Objectives and background: The expression of inflammatory genes in the heart plays an important role in organ dysfunction. However, the contribution of cardiomyocytes to this process, and in particular to the synthesis of high concentrations of nitric oxide and Prostaglandins, has not been analyzed in detail. For this reason, cultured isolated cardiomyocytes were used to evaluate the response to pro-inflammatory stimuli. Methods and results: Isolated cultured foetal, neonatal, and adult rat cardiomyocytes were stimulated with lipopolysaccharide and cytokines, and the expression of nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) in these cells was investigated. Only cultured foetal cardiomyocytes expressed NOS-2 and COX-2 under these conditions, whereas the neonatal counterparts required various days in culture to gain this response. Analysis of the NF-kappaB signalling pathway showed an impaired activation of IkappaB kinase in response to lipopolysaccharide and cytokines in cells maintained in culture for I day. These data were confirmed by DNA microarray analysis. However, other early signalling pathways, such as the p38 and Erk MAPKs, were not affected by the time in culture. Conclusions: Neonatal and adult cardiomyocytes are resistant to the expression of pro-inflammatory genes due to impairment in the activation of IkappaB kinase, a process that might contribute to preventing rapid organ dysfunction in the course of various inflammatory pathologies, such as septic shock and myocarditis. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.