TRAIL: a multifunctional cytokine.

نویسندگان

  • Uta Schaefer
  • Oksana Voloshanenko
  • Daniela Willen
  • Henning Walczak
چکیده

The Tumor necrosis factor (TNF)-Related Apoptosis Inducing Ligand, TRAIL, has gained much attention due to its specific anti-tumor potential without toxic side effects. TRAIL binds to a complex receptor system. In humans there are two death-inducing receptors for TRAIL while only one is present in mice. The signaling induced by these receptors leads to apoptosis but might also result in activation of survival signals. To assess the safety and possible side effects of TRAIL-based cancer therapy it is necessary to understand the physiological role of the TRAIL/TRAIL-R system. This has been addressed in mice deficient either for TRAIL or for its only murine apoptosis-inducing receptor, TRAIL-R (MK/mDR5). In this review we will discuss their phenotypes and the results of recent studies on the role of TRAIL in the homeostasis of the immune system, the influence of the TRAIL/TRAIL-R system on infection and autoimmune diseases and the still controversial role of TRAIL in tumorigenesis. Clinical trials with TRAIL and other TRAIL receptor agonists are now under way. It will be exciting to determine which TRAIL-R agonists, either alone or in combination with other anti-cancer therapeutics, will result in better outcome of cancer treatment in the future.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Effect of tumor necrosis factor-related apoptosis-inducing ligand on the reduction of joint inflammation in experimental rheumatoid arthritis.

This study focused on the potential therapeutic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on collagen-induced arthritis (CIA) and on the elucidation of the mechanisms involved. DBA/1J mice with established CIA were treated with various amount of recombinant soluble human TRAIL. The effects of TRAIL on the development and severity of CIA in this DBA/1J mouse model...

متن کامل

The TRAIL-Induced Cancer Secretome Promotes a Tumor-Supportive Immune Microenvironment via CCR2

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known for specifically killing cancer cells, whereas in resistant cancers, TRAIL/TRAIL-R can promote metastasis via Rac1 and PI3K. It remains unknown, however, whether and to what extent TRAIL/TRAIL-R signaling in cancer cells can affect the immune microenvironment. Here we show that TRAIL-triggered cytokine secretion from...

متن کامل

Cytokines and BCR-ABL mediate suppression of TRAIL-induced apoptosis through inhibition of forkhead FOXO3a transcription factor.

Cytokine-provided survival signals are known to suppress apoptosis through inhibition of mitochondrial pathways that involve Bcl-2 family members. Here we show that in hematopoietic cells, cytokines also regulate death receptor-mediated pathways. We demonstrate that hematopoietic cytokines such as IL-3 and erythropoietin in normal cells, as well as BCR-ABL oncoprotein in transformed cells, inhi...

متن کامل

TRAIL-R as a negative regulator of innate immune cell responses.

TRAIL receptor (TRAIL-R) signaling has been implicated in inducing apoptosis in tumor cells, but little is understood about its physiological function. Here, we report the generation and characterization of TRAIL-R(-/-) mice, which develop normal lymphocyte populations but possess enhanced innate immune responses. TRAIL-R(-/-) mice exhibited increased clearance of murine cytomegalovirus that co...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Frontiers in bioscience : a journal and virtual library

دوره 12  شماره 

صفحات  -

تاریخ انتشار 2007