Abstract
Objective Chemokines control the migration of leukocytes to inflamed tissue, and in particular monocyte chemoattractant protein (MCP)-1 has been implicated in the pathogenesis of several cardiovascular disorders such as chronic heart failure (CHF) and myocarditis. We hypothesised that MCP-1 may directly contribute to an inflammatory response in the cardiomyocytes, and in the present study we examined in adult rat cardiomyocytes: (i) the effect of tumour necrosis factor (TNF)a on MCP-1 production, (ii) the effect of MCP-1 on production of other inflammatory cytokines, and (iii) if the anti-inflammatory cytokine interleukin (IL)-10 could suppress any TNFα-induced MCP-1 production. Methods We used enzyme immunoassays, RNase protection assays and slot blot analysis to measure protein and mRNA levels of various cytokines in adult rat cardiomyocyte cultures. Results (i) We found a ∼6.4-fold increase of the MCP-1 level accompanied by an increase in MCP-1 mRNA accumulation in cardiomyocyte cultures after TNFα stimulation. (ii) In contrast, TNFα had no effect on IL-10 and only a modest effect on IL-1β and IL-6 levels in these cells. (iii) Importantly, MCP-1 stimulated inflammatory response in cardiomyocytes by enhancing IL-1β and IL-6 levels in these cells as found at both the protein and mRNA level. (iv) Co-stimulation with IL-10 resulted in a ∼55 % reduction in TNFα-stimulated MCP-1 levels in cardiomyocyte culture supernatants. Conclusion The present study demonstrates for the first time that MCP-1 can directly affect cardiomyocytes, and we introduce MCP-1 as a potential enhancer and IL-10 as a potential suppresser of inflammatory responses within the myocardium.
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Received: 10 October 2000 / Returned for 1. revision: 2 November 2000 / 1. Revision received: 5 December 2000 / Returned for 2. revision: 2 January 2001 / 2. Revision received: 5 January 2001 / Accepted: 8 January 2001
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Damås, J., Aukrust, P., Ueland, T. et al. Monocyte chemoattractant protein-1 enhances and interleukin-10 suppresses the production of inflammatory cytokines in adult rat cardiomyocytes. Basic Res Cardiol 96, 345–352 (2001). https://doi.org/10.1007/s003950170042
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DOI: https://doi.org/10.1007/s003950170042