Mycophenolate Mofetil and Rapamycin Induce Apoptosis in the Human Monocytic U937 Cell Line Through Two Different Pathways. Issue 10 (24th April 2017)

• Record Type: Journal Article
• Authors: Nowak, Maxime; Tardivel, Sylviane; Nguyen‐Khoa, Thao; Abreu, Sonia; Allaoui, Fatima; Fournier, Natalie; Chaminade, Pierre; Paul, Jean‐Louis; Lacour, Bernard
• Is Part Of: Journal of cellular biochemistry. Volume 118:Issue 10(2017)
• Page Start: 3480
• Page End: 3487
• Publication Date: 2017-04-24
• Subjects: APOPTOSIS -- IMMUNOSUPPRESSIVE DRUG -- LIPOPROTEIN -- MONOCYTE -- ATHEROSCLEROSIS -- TRANSPLANTATION; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.26007
• Languages: English
• ISSNs: 0730-2312

Abstract

ABSTRACT: Transplant vasculopathy may be considered as an accelerated form of atherosclerosis resulting in chronic rejection of vascularized allografts. After organ transplantation, a diffuse intimal thickening is observed, leading to the development of an atherosclerosis plaque due to a significant monocyte infiltration. This results from a chronic inflammatory process induced by the immune response. In this study, we investigated the impact of two immunosuppressive drugs used in therapy initiated after organ transplantation, mycophenolate mofetil, and rapamycin, on the apoptotic response of monocytes induced or not by oxidized LDL. Here we show the pro‐apoptotic effect of these two drugs through two distinct signaling pathways and we highlight a synergistic effect of rapamycin on apoptosis induced by oxidized LDL. In conclusion, since immunosuppressive therapy using mycophenolate mofetil or rapamycin can increase the cell death in a monocyte cell line, this treatment could exert similar effects on human monocytes in transplant patients, and thus, prevent transplant vasculopathy, atherosclerosis development, and chronic allograft rejection. J. Cell. Biochem. 118: 3480–3487, 2017. © 2017 Wiley Periodicals, Inc. Abstract : This study highlight the pro‐apoptotic effect of two major immunosuppressive drugs commonly used in post‐transplant therapy, mycophenolate mofetil, and rapamycin. We demonstrate that rapamycin has a significant effect for potentiating the monocyte apoptosis induced by oxLDL, and thus, could prevent the development of atherosclerosis and limit the transplant rejection.