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Cardiac dysfunction in StrepTSS: group A streptococcus disrupts the directional cardiomyocyte-to-macrophage crosstalk that maintains macrophage quiescence.
- Source :
-
Cytokine [Cytokine] 2012 Jul; Vol. 59 (1), pp. 191-4. Date of Electronic Publication: 2012 Apr 23. - Publication Year :
- 2012
-
Abstract
- Myocardial dysfunction in group A streptococcal (GAS) toxic shock syndrome (StrepTSS) is characterized by severe biventricular dilatation and a striking reduction in ventricular performance; however, the mechanisms have not been fully elucidated. We have previously shown that pro-inflammatory cytokines are upregulated in the hearts of experimental animals with GAS bacteremia and that cardiomyocytes themselves as well as macrophages are the principal cytokine sources. Although macrophage-derived cytokines can clearly affect cardiac contractility, we questioned whether soluble cardiomyocyte-derived mediators might in turn affect macrophage function. Thus, we sought evidence of cardiomyocyte-to-macrophage directional cross-talk under resting versus GAS-stimulated conditions, using production of matrix metalloproteinase-9 (MMP-9) as an indicator of such signaling. Our results demonstrate that unstimulated cardiomyocytes produce a soluble inhibitor/s that maintains macrophage functional quiescence. Further, viable GAS induced production of cardiomyocyte-derived stimulator/s that overcomes quiescence and boosts macrophages production of MMP-9 and expression of pro-inflammatory cytokines (IL-1β, IL-6) and cardiodepressant factors (iNOS). Understanding the role of these cardiomyocyte-derived effectors of macrophage function (herein termed "cardiokines") in sepsis-associated cardiomyopathy may suggest new targets for therapeutic intervention.<br /> (Published by Elsevier Ltd.)
- Subjects :
- Animals
Cell Line
Down-Regulation
Macrophages enzymology
Matrix Metalloproteinase 9 biosynthesis
Mice
Myocytes, Cardiac microbiology
Solubility
Heart physiopathology
Macrophages metabolism
Macrophages microbiology
Myocytes, Cardiac metabolism
Shock, Septic microbiology
Shock, Septic physiopathology
Streptococcus pyogenes physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0023
- Volume :
- 59
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cytokine
- Publication Type :
- Academic Journal
- Accession number :
- 22534112
- Full Text :
- https://doi.org/10.1016/j.cyto.2012.03.023