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Mycophenolate Mofetil and Rapamycin Induce Apoptosis in the Human Monocytic U937 Cell Line Through Two Different Pathways
Author(s) -
Nowak Maxime,
Tardivel Sylviane,
NguyenKhoa Thao,
Abreu Sonia,
Allaoui Fatima,
Fournier Natalie,
Chaminade Pierre,
Paul JeanLouis,
Lacour Bernard
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26007
Subject(s) - mycophenolate , apoptosis , u937 cell , cell culture , thp1 cell line , microbiology and biotechnology , cancer research , chemistry , biology , medicine , biochemistry , genetics , transplantation
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.