BACKGROUND: Dendritic cells induce tolerance in the immature state besides the function of antigen presenting cells in the mature state. Using this effect, it will be overcome the rejection in organ transplantation. In this research we are to confirm the tolerance effect and induction mechanism in immature dendritic cell cultured with low-dose GM-CSF. METHODS: Dendritic cells were cultured from BALB/c (H-2d) bone marrow cells in the low concentration of GM-CSF (5U/mL, GM(lo)DC) for 10 days. The phenotype and functional properties of these GM(lo)DC were compared to those of standard BM-DC cultures generated in the high concentrations of GM-CSF (200U/mL) with lipopolysaccharide (GM(hi)DC). RESULTS: Compare to mature DC, GM(lo)DC expressed the low level of CD80 and CD86 and these cells were weak stimulators of allogeneic T cell responses by mixed lymphocyte reaction. The administration of GM(lo)DC prolonged allogeneic skin graft survival (median survival time 11.3+/-1.2 days, compared with 6.6+/-0.8 days in nontreated controls). The effects of these cells were donor specific but couldn't be sustained for a long period. CONCLUSIONS: GM(lo)DC were phenotypically immature and they didn't induce allogeneic T cell responses compared with GM(hi)DC in vitro. It is suggested that the less expression of costimulatory molecule in GM(lo)DC induce the tolerance effect.
Antigen-Presenting Cells ; Bone Marrow Cells ; Dendritic Cells* ; Graft Survival ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Humans ; Immune Tolerance* ; Lymphocyte Culture Test, Mixed ; Organ Transplantation ; Phenotype ; Skin ; Tissue Donors ; Transplants

The efficacy and side effects associated with anticancer drugs have attracted an extensive research focus. Onconephrology is an evolving field of nephrology that deals with the study of kidney diseases in cancer patients. Most renal diseases in cancer patients are unique, and management of renal disease can be challenging especially in the presence of continuing use of the nephrotoxic drugs. Cisplatin is one of the most important chemotherapeutic agents used in the treatment of various malignancies, such as head, neck, ovarian, and cervical cancers. The major limitation in the clinical use of cisplatin is its tendency to induce adverse effects, such as nephrotoxicity. Recently, plant-derived phytochemicals have emerged as novel agents providing protection against cisplatin-induced renal cytotoxicity. Owing to the diversity of phytochemicals, they cover a wide spectrum of therapeutic indications in cancer and inflammation and have been a productive source of lead compounds for the development of novel medications. Of these agents, the effectiveness of triterpenoids, isolated from various medicinal plants, against cisplatin-induced renal cytotoxicity has been reported most frequently compared to other phytochemicals. Triterpenes are one of the most numerous and diverse groups of plant natural products. Triterpenes ameliorate cisplatin-induced renal damage through multiple pathways by inhibiting reactive oxygen species, inflammation, down-regulation of the MAPK, apoptosis, and NF-κB signaling pathways and upregulation of Nrf2-mediated antioxidant defense mechanisms. Here, we reviewed recent findings on the natural compounds with protective potential in cisplatin-induced renal cytotoxicity, provided an overview of the protective effects and mechanisms that have been identified to date, and discussed strategies to reduce renal cytotoxicity induced by anticancer drugs.