TREM-1 inhibition attenuates inflammation and tumor within the colon

Int Immunopharmacol. 2013 Oct;17(2):155-61. doi: 10.1016/j.intimp.2013.06.009. Epub 2013 Jun 25.

Abstract

The role of myeloid cell receptor TREM-1 as an amplifier of inflammation has been widely accepted and more interestingly, TREM-1 has been implicated in tumorigenesis. However, it is not clear whether TREM-1 links colon inflammation and tumor in vivo. This study aimed to investigate whether inhibition of proinflammatory TREM-1 would prevent aberrant inflammation and tumor development within the colon. In the present study, the mouse model of DSS-induced colitis and colitis-associated tumorigenesis was used. In vivo, the treatment with the TREM-1 antagonist LP17 or control peptide was initiated at the beginning of or after induction of experimental colitis or colitis-associated tumorigenesis. As a result, TREM-1 inhibition by LP17 treatment ameliorated the development of inflammation and tumor within the colon through exerting anti-inflammatory effects. In addition, LP17 decreased intestinal epithelial proliferation in DSS-induced colitis. Taken together, TREM-1 plays critical roles in colon inflammation and tumor and targeting TREM-1 may represent a novel therapeutic strategy for colon inflammation and associated cancer.

Keywords: Colon; Inflammation; TREM-1; Tumor development.

MeSH terms

  • Animals
  • Carcinogenesis*
  • Colitis / chemically induced
  • Colitis / complications
  • Colitis / immunology*
  • Colon / drug effects
  • Colon / pathology
  • Colonic Neoplasms / etiology*
  • Dextran Sulfate / administration & dosage
  • Disease Models, Animal
  • Membrane Glycoproteins / antagonists & inhibitors*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Molecular Targeted Therapy*
  • Myeloid Cells / immunology*
  • Peptide Fragments / pharmacology*
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Immunologic / metabolism
  • Triggering Receptor Expressed on Myeloid Cells-1

Substances

  • Membrane Glycoproteins
  • Peptide Fragments
  • Receptors, Immunologic
  • TREM1 protein, mouse
  • Triggering Receptor Expressed on Myeloid Cells-1
  • Dextran Sulfate