| The medicinal plant Tripterygium Wilfordii Hook F. (TWHF) extracts have, for many years, been used widely to treat autoimmune diseases including rheumatoid arthritis, immune complex nephritis, and systemic lupus erythematosus (SLE) in China. Triptolide, a diterpene triepoxide, is an active component of extracts derived from Tripterygium, and has anti-inflammatory, immunosuppressive, antiproliferative and proapoptotic activity. Due to its potent anti-inflammatory and immunosuppressive properties, In organ transplantation, both clinical and experimental studies have demonstrated that triptolide effectively prolongs allograft survival. Triptolide can also induce apoptosis of tumor cells, via the p53 pathway and NF-κB and AP-1 transcriptional activity. Whereas the responses of T cells to triptolide treatment are reasonably well characterized, there are few reports concerning the effect of triptolide on other kinds of immune cells, such as dendritic cells (DC). Investigation of how triptolide affects other immune cells, particularly those which interact with T cells, will aid in the full elucidation of the mechanism by which triptolide mediates anti-inflammatory and immunosuppressive effects in vivo.DCs are the most potent professional antigen-presenting cells (APC) that are critical for the induction of both immune responses and immune tolerance. DCs originate from bone marrow precursors, migrating through the blood stream to almost every tissue, where they reside as immature DC, specializing in antigen uptake. Encounters with microbial components (LPS, CpG,PMA, etc.), proinflammatory cytokines (TNF-(, IFN-( etc.), or T-cells (CD40 ligand) can trigger DC to mature. Maturing DC up-regulate expression of major histocompatibility complex class I and class II molecules (MHC-I and MHC-II) and costimulatory molecules, acquiring the capacity to present processed antigens to T cells. Upon maturation, DCs migrate from peripheral tissues to the T-cell areas of draining lymphoid organs, where they encounter na?ve T cells and initiate adaptive immune response. It is well established that initiation of immune responses or tolerance induction by DC is strictly dependent on DC maturation state. Whereas mature DC activate T cell responses, immature DC have the potential to induce immune tolerance by inhibiting the proliferation of alloreactive T cells, inducing antigen-specific T cell anergy or triggering the generation of regulatory T cells. Therefore, the inhibition of DC function at different stages of DC differentiation or maturation, during migration, or interaction with T cells, or the maintenance of DC in the immature state, could all be mechanisms by which anti-inflammatory and immunosuppressive drugs exert their effects. Over 50~70% of solid tumors harbor mutations in p53, which confers relative chemoresistance. TNF family members such as TNF-α, Fas, and TNF-related apoptosis-inducing ligand, also known as Apo2L, induce apoptosis in tumor cells regardless of the p53 phenotype. Unfortunately, TNF-α-induced apoptosis is limited by activation of NF-?B. Additionally, activation of NF-?B induces the release of pro-inflammatory cytokines, which damage the host. It has reported that triptolide can sensitize tumor cells to TNF-α-induced apoptosis through inhibition of NF-?B. There are also studies that show triptolide is cytotoxic in leukemia and breast cancer cell lines. But there are also reported that triptolide can induce activatived T cells apoptosis, So, we want to know wheather triptolide alone or cooperates with TNF-α can induce apoptosis in tumor cell lines at a non-cytotoxic concentration. [Objective] The present investigation included two purposes: the first was that triptolide regulates the functions and induces apoptosis of dendritic cell; the other was that triptolide inhibit tumor cells proliferation and indue apoptosis in vitro and vivo. [Methods] (1) The expression of DC surface marker and chemokine receptor was examined by FACSCalibur flow cytometry. (2) Reverse transcriptase polymerase...
|
PDF Full Text Request