Pathophysiological role of guanylate-binding proteins in gastrointestinal diseases

World J Gastroenterol. 2016 Jul 28;22(28):6434-43. doi: 10.3748/wjg.v22.i28.6434.

Abstract

Guanylate-binding proteins (GBPs) are interferon-stimulated factors involved in the defense against cellular pathogens and inflammation. These proteins, particularly GBP-1, the most prominent member of the family, have been established as reliable markers of interferon-γ-activated cells in various diseases, including colorectal carcinoma (CRC) and inflammatory bowel diseases (IBDs). In CRC, GBP-1 expression is associated with a Th1-dominated angiostatic micromilieu and is correlated with a better outcome. Inhibition of tumor growth by GBP-1 is the result of its strong anti-angiogenic activity as well as its direct anti-tumorigenic effect on tumor cells. In IBD, GBP-1 mediates the anti-proliferative effects of interferon-γ on intestinal epithelial cells. In addition, it plays a protective role on the mucosa by preventing cell apoptosis, by inhibiting angiogenesis and by regulating the T-cell receptor signaling. These functions rely to a large extent on the ability of GBP-1 to interact with and remodel the actin cytoskeleton.

Keywords: Colorectal carcinoma; Guanylate-binding proteins; Inflammatory bowel diseases; Interferon.

Publication types

  • Review

MeSH terms

  • Apoptosis / immunology
  • Cell Proliferation
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / metabolism
  • GTP-Binding Proteins / immunology*
  • GTP-Binding Proteins / metabolism
  • Humans
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / metabolism
  • Interferon-gamma / immunology*
  • Interferon-gamma / metabolism
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / metabolism
  • Prognosis
  • Receptors, Antigen, T-Cell / immunology
  • Th1 Cells / immunology

Substances

  • GBP1 protein, human
  • Receptors, Antigen, T-Cell
  • Interferon-gamma
  • GTP-Binding Proteins