Effect of immunosuppression on the human mesangial cell cycle

Abstract

The present study investigated the effects of immunosuppressive agents [tacrolimus (Tac), cyclosporine A (CsA), mycophenolic acid (MMF) and methylprednisone (MP)] on the proliferation, cell cycle progression and apoptotic rate of human mesangial cells. Cultured human mesangial cells were treated with several concentrations of the immunosuppressive agents for 24, 48 or 72 h. Cell cycle progression, proliferation and apoptosis were analyzed using an MTT assay and flow cytometry. Tac and CsA significantly inhibited the proliferation of human mesangial cells in a dose- and time-dependent manner. Cell cycle analysis revealed that Tac and CsA arrested mesangial cells in the G0/G1 phase, preventing them from entering S phase. Similarly, MP inhibited human mesangial cell growth by causing cell cycle arrest in G0/G1 phase. MMF also inhibited mesangial cell proliferation, but accomplished this by preventing progression from S phase to the G2/M phase. The combination of MP and MMF synergistically inhibited mesangial cell proliferation. Tac, CsA, MP and MMF inhibited proliferation of human mesangial cells by blocking progression of the cell cycle. In conclusion, these agents, sequentially or in combination, may be used to effectively treat mesangial proliferative glomerular disease.

Microwave-assisted extraction, characterization and immunomodulatory activity on RAW264.7 cells of polysaccharides from Trichosanthes kirilowii Maxim seeds

“…Several studies suggested that the overzealous immune responses associated with macrophage activation syndrome (MAS) or cytokine storm, also known as secondary haemophagocytic lymphohistocytosis (sHLH), may be driving COVID-19 related ARDS [ [3] , [4] , [5] ]. Although several immunosuppressants have been found, most of them have side effects, such as cyclosporine, Tacrolimus [ 6 ], methylprednisone [ 7 ], etc. Therefore, it is crucial to find a natural immunosuppressive agent.…”

Quantitative phosphoproteomics to unravel the cellular response to chemical stressors with different modes of action

“…These breaks have been suggested to arise from SSB during DNA replication and were suggested to result from a general inability to repair DSBs (Zhang et al 2006). Specific CsA responses at the phosphoproteome level include the down-regulation of pathways that control hematopoietic differentiation and immunity (Granzyme B, ErbB2, NGF, Rho GTPase, AML) being consistent with known effects of CsA as an immunosuppressant (Zhou et al 2015) and inducer of apoptosis (Koppelstaetter et al 2018). Differential phosphorylation responses of DNA damage response-related proteins.…”

Regulation of Proliferation by a Mitochondrial Potassium Channel in Pancreatic Ductal Adenocarcinoma Cells

“…In sharp contrast with the effect of Shk and clofazimine on cell cycle progression, the mitochondriotropic Kv1.3 inhibitors slightly increased proliferation when used at low concentrations, as indicated by the increase and decrease of the percentage of cells in S phase and G0/G1 phase, respectively. On the other hand, the same drugs seems to block proliferation of Colo357 cells, by preventing progression from S phase to the G2/M phase ( 44 ). Although knock-down of VDAC1 was shown to reduce proliferation in HeLa cells ( 45 ), for the major part of mitochondrial ion channels, their possible involvement in the regulation of cell cycle progression has not been addressed, to our best knowledge.…”