Jk. Damas et al., Monocyte chemoattractant protein-1 enhances and interleukin-10 suppresses the production of inflammatory cytokines in adult rat cardiomyocytes, BAS R CARD, 96(4), 2001, pp. 345-352
Objective Chemokines control the migration of leukocytes to inflamed tissue
, and in particular monocyte chemoattractant protein (MCP)-1 has been impli
cated in the pathogenesis of several cardiovascular disorders such as chron
ic heart failure (CHF) and myocarditis. We hypothesised that MCP-1 may dire
ctly contribute to an inflammatory response in the cardiomyocytes, and in t
he 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 TNF alpha -in
duced MCP-1 production. Methods We used enzyme immunoassays, RNase protecti
on assays and slot blot analysis to measure protein and mRNA levels of vari
ous cytokines in adult rat cardiomyocyte cultures. Results (i) We found a s
imilar to6.4-fold increase of the MCP-1 level accompanied by an increase in
MCP-1 mRNA accumulation in cardiomyocyte cultures after TNF alpha stimulat
ion. (ii) In contrast, TNF alpha had no effect on IL-10 and only a modest e
ffect on IL-1 beta and IL-6 levels in these cells. (iii) Importantly, MCP-1
stimulated inflammatory response in cardiomyocytes by enhancing IL-1 beta
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 similar to 55% reduction in T
NF alpha -stimulated MCP-1 levels in cardiomyocyte culture supernatants. Co
nclusion The present study demonstrates for the first time that MCP-1 can d
irectly affect cardiomyocytes, and we introduce MCP-1 as a potential enhanc
er and IL-10 as a potential suppresser of inflammatory responses within the
myocardium.