کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2794476 | 1155285 | 2012 | 4 صفحه PDF | دانلود رایگان |

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.
► Cardiomyocytes (CM) produce soluble inhibitor/s of macrophage (Mϕ) MMP-9 production.
► CM-to-Mϕ crosstalk exists and favors broad macrophage functional quiescence.
► Streptococcus pyogenes overcomes CM-induced Mϕ quiescence and elicits CM-derived Mϕ activator/s.
► Paracrine CM-derived Mϕ activators/inhibitors are herein termed cardiokines.
► S. pyogenes-stimulated cardiokines may mediate early events in StrepTSS cardiomyopathy.
Journal: Cytokine - Volume 59, Issue 1, July 2012, Pages 191–194