Immunosuppression in cardiac graft rejection: A human in vitro model to study the potential use of new immunomodulatory drugs
- Center for Research Transfer and High Education 'DENOthe', University of Florence, Florence (Italy)
- Department of Physiological Sciences, University of Florence, Florence (Italy)
- Department of Surgery and Bioengineering, University of Siena, Siena (Italy)
- Department of Anatomy, Histology and Forensic Medicine, University of Florence, Florence (Italy)
CXCL10-CXCR3 axis plays a pivotal role in cardiac allograft rejection, so that targeting CXCL10 without inducing generalized immunosuppression may be of therapeutic significance in allotransplantation. Since the role of resident cells in cardiac rejection is still unclear, we aimed to establish reliable human cardiomyocyte cultures to investigate Th1 cytokine-mediated response in allograft rejection. We used human fetal cardiomyocytes (Hfcm) isolated from fetal hearts, obtained after legal abortions. Hfcm expressed specific cardiac lineage markers, specific cardiac structural proteins, typical cardiac currents and generated ventricular action potentials. Thus, Hfcm represent a reliable in vitro tool for allograft rejection research, since they resemble the features of mature cells. Hfcm secreted CXCL10 in response to IFN{gamma} and TNF{alpha}{alpha}; this effect was magnified by cytokine combination. Cytokine synergy was associated to a significant TNF{alpha}-induced up-regulation of IFN{gamma}R. The response of Hfcm to some currently used immunosuppressive drugs compared to rosiglitazone, a peroxisome proliferator-activated receptor {gamma} agonist and Th1-mediated response inhibitor, was also evaluated. Only micophenolic acid and rosiglitazone halved CXCL10 secretion by Hfcm. Given the pivotal role of IFN{gamma}-induced chemokines in Th1-mediated allograft rejection, these preliminary results suggest that the combined effects of immunosuppressive agents and rosiglitazone could be potentially beneficial to patients receiving heart transplants.
- OSTI ID:
- 21045961
- Journal Information:
- Experimental Cell Research, Vol. 314, Issue 6; Other Information: DOI: 10.1016/j.yexcr.2007.12.016; PII: S0014-4827(07)00595-2; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
Similar Records
CD14{sup +} monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells
IGF-1 resist oxidative damage to HaCaT and depigmentation in mice treated with H2O2