Mycophenolate Mofetil and Rapamycin Induce Apoptosis in the Human Monocytic U937 Cell Line Through Two Different Pathways

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.

Mechanism Exploration on the Immunoregulation of Allogeneic Heart Transplantation Rejection in Rats With Exosome miRNA and Proteins From Overexpressed IDO1 BMSCs

“…Subsequently, function enrichment analyses were performed on these immune mRNAs of IDO1-related differential miRNAs, finding that enrichment results mainly in the regulation of inflammatory response, lipid and atherosclerosis, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, and so on. Previous research has discovered the relationship between organ transplantation and atherosclerosis, where organ transplantation leads the development 61 . TNF has been confirmed as a key factor that regulates cell inflammation response and mediates tumor rejection 62 .…”

The Effects of Immunosuppressive Drugs on the Characteristics and Functional Properties of Bone Marrow-Derived Stem Cells Isolated from Patients with Diabetes Mellitus and Peripheral Arterial Disease

“…Vitiallo et al proved that mammalian targets of rapamycin inhibitors (siromimus and everolimus) showed a very potent anti-inflammatory effect by decreasing the response of neutrophils and decreasing both release of VEGF and IL-8 [23]. Moreover, Nowak et al demonstrated the pro-apoptotic effect of sirolimus induced by oxidized LDL as well as mycophenolate mofetil-both drugs significantly increased the cell death in a monocyte cell lineage [24]. To our knowledge, there are no trials assessing the impact of IS drugs on the functional properties of hematopoietic stem cells; most of the studies are focused on the transplantation of these cells in the treatment of hematological diseases.…”

Mycophenolate Mofetil Alone and in Combination with Tacrolimus Inhibits the Proliferation of HT-29 Human Colonic Adenocarcinoma Cell Line and Might Interfere with Colonic Tumorigenesis

“…For experimental purposes, cells were treated with tacrolimus (0.1 μM and 1 μM), MMF (1 or 10 μg/ml) or a combination of tacrolimus and MMF (0.1 μM and 1 μg/ml, 0.1 μM and 10 μg/ml, 1 μM and 1 μg/ml, and 1 μM and 10 μg/ml, respectively) as described elsewhere (7,8). Control cells were treated with vehicle alone.…”