ausblenden:
Schlagwörter:
TUMOR-NECROSIS-FACTOR; SMOOTH-MUSCLE-CELLS; BONE-MARROW; STROMAL CELLS;
FAILURE; THERAPY; ETANERCEPT; ACTIVATION; MECHANISMS; EXPRESSIONCardiovascular System & Cardiology; Mesenchymal stem cells; Proteomics; TNF-alpha; Fibrosis; Inflammation;
Heart failure; Acute lung injury;
Zusammenfassung:
Mesenchymal stem cells ( MSC) have been used to treat different clinical conditions although the mechanisms by which pathogenetic processes are affected are still poorly understood. We have previously analyzed the homing of bone marrow-derived MSC to diseased tissues characterized by a high degree of mononuclear cell infiltration and postulated that MSC might modulate inflammatory responses. Here, we demonstrate that MSC mitigate adverse tissue remodeling, improve organ function, and extend lifespan in a mouse model of inflammatory dilative cardiomyopathy ( DCM). Furthermore, MSC attenuate Lipopolysaccharide-induced acute lung injury indicating a general role in the suppression of inflammatory processes. We found that MSC released sTNF-RI, which suppressed activation of the NFjBp65 pathway in cardiomyocytes during DCM in vivo. Substitution of MSC by recombinant soluble TNF-R partially recapitulated the beneficial effects of MSC while knockdown of TNF-R prevented MSC-mediated suppression of the NFjBp65 pathway and improvement of tissue pathology. We conclude that sTNF-RI is a major part of the paracrine machinery by which MSC effect local inflammatory reactions.
