Expression of receptor interacting protein 3 and mixed lineage kinase domain-like protein-key proteins in necroptosis is upregulated in ulcerative colitis

Ann Palliat Med. 2019 Sep;8(4):483-489. doi: 10.21037/apm.2019.07.04. Epub 2019 Aug 12.

Abstract

Background: Ulcerative colitis (UC) is a chronic inflammatory colonic disease strongly associated with intestinal epithelial cell (IEC) death. Necroptosis is characterized by a newly programmed cell death through a caspase-independent pathway. Receptor interacting protein 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) are very important in the pathway of necroptosis. However, their expression in UC remains unelucidated. This study aimed to investigate the expression of RIP3 and MLKL in patients with UC, along with its correlation with disease activity.

Methods: Colonic tissue samples were taken from 22 UC patients and 19 healthy controls. RIP3 and MLKL expression levels were evaluated by immunohistochemical staining and western blotting.

Results: RIP3 and MLKL were upregulated in inflamed tissues of UC (P<0.01). No variations were observed in healthy control subjects and non-inflamed colons (P>0.05). RIP3 and MLKL were positively correlated with UC disease activity (P<0.01).

Conclusions: Our results suggest that necroptosis is strongly associated with intestinal inflammation in patients with UC. Further studies of necroptosis may be helpful in future treatments of UC.

Keywords: Ulcerative colitis (UC); intestinal inflammation; mixed lineage kinase domain-like protein (MLKL); receptor interacting protein 3 (RIP3).

MeSH terms

  • Adult
  • Case-Control Studies
  • Colitis, Ulcerative / metabolism*
  • Female
  • Humans
  • MAP Kinase Kinase Kinases / metabolism
  • Male
  • Middle Aged
  • Necroptosis / physiology*
  • Protein Kinases / metabolism*
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*
  • Up-Regulation / physiology
  • Young Adult

Substances

  • MLKL protein, human
  • Protein Kinases
  • RIPK3 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • MAP Kinase Kinase Kinases
  • MAP3K13 protein, human