title: Monocyte chemoattractant protein-1 enhances and interleukin-10 suppresses the production of inflammatory cytokines in adult rat cardiomyocytes.
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)alpha 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 TNFalpha-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 approximately 6.4-fold increase of the MCP-1 level accompanied by an increase in MCP-1 mRNA accumulation in cardiomyocyte cultures after TNFalpha stimulation. (ii) In contrast, TNFalpha had no effect on IL-10 and only a modest effect on IL-1beta and IL-6 levels in these cells. (iii) Importantly, MCP-1 stimulated inflammatory response in cardiomyocytes by enhancing IL- 1beta and IL-6 levels in these cells as found at both the protein and mRNA level. (iv) Co-stim-ulation with IL-10 resulted in a approximately 55% reduction in TNFalpha-stimulated MCP-1 levels in cardiomyocyte culture supernatants.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Research Institute for Internal Medicine, Rikshospitalet, Oslo, Norway. j.k.damas@klinmed.uio.no
authors.forename: J K
authors.initials: JK
authors.lastname: Damås
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
authors.forename: T
authors.initials: T
authors.lastname: Ueland
authors.forename: A
authors.initials: A
authors.lastname: Odegaard
authors.forename: H G
authors.initials: HG
authors.lastname: Eiken
authors.forename: L
authors.initials: L
authors.lastname: Gullestad
authors.forename: O M
authors.initials: OM
authors.lastname: Sejersted
authors.forename: G
authors.initials: G
authors.lastname: Christensen
mesh_terms: D000818:Animals; D002469:Cell Separation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology / Q000502:physiology*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10