Following the TRAIL to apoptosis

Immunol Res. 2006;35(3):249-62. doi: 10.1385/IR:35:3:249.

Abstract

Apoptosis, programmed cell death, eliminates injured or harmful cells. It can mediate its response through the actions of death ligands including TRAIL. TRAIL, a member of TNF superfamily, induces apoptosis of transformed cells through the action of death domain receptors DR-4 and DR5. It directly induces apoptosis through an extrinsic pathway, which involves the activation of caspases. TRAIL also is able to prevent apoptosis through the actions of its decoy receptors DcR-1 and DcR-2. Various regulators of TRAIL include FADD, IAPs, Bcl-2s, p53, and FLIPs. TRAIL is present in cells involved in asthma including eosinophils, mast cells, fibroblasts, and airway epithelial cells. It is expressed in airway remodeling and may be linked with the pathways of transforming growth factor-beta1, which is thought to cause damage to the epithelium. The repair process of the epithelium is hindered as a result of increased apoptosis induced by TGF-beta1, which overlaps with the pathways of TRAIL. Analogs of TRAIL could have therapeutical applications for asthma. TRAIL is also seen as the basis for a "miracle" drug for cancer because of its ability to selectively kill cancer cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / metabolism
  • Asthma / immunology
  • Asthma / metabolism
  • Asthma / physiopathology*
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Signal Transduction / physiology*
  • TNF-Related Apoptosis-Inducing Ligand* / metabolism
  • TNF-Related Apoptosis-Inducing Ligand* / therapeutic use

Substances

  • Apoptosis Regulatory Proteins
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • TNF-Related Apoptosis-Inducing Ligand