Analysis of SHIP1 expression and activity in Crohn's disease patients

PLoS One. 2017 Aug 2;12(8):e0182308. doi: 10.1371/journal.pone.0182308. eCollection 2017.

Abstract

Background: SH2 domain containing inositol-5-phosphatase (SHIP1) is an important modulator of innate and adaptive immunity. In mice, loss of SHIP1 provokes severe ileitis resembling Crohn's disease (CD), as a result of deregulated immune responses, altered cytokine production and intestinal fibrosis. Recently, SHIP1 activity was shown to be correlated to the presence of a CD-associated single nucleotide polymorphism in ATG16L1. Here, we studied SHIP1 activity and expression in an adult cohort of CD patients.

Methods: SHIP1 activity, protein and mRNA expression in peripheral blood mononuclear cells from CD patients in clinical remission were determined by Malachite green assay, Western blotting and qRT-PCR respectively. Genomic DNA was genotyped for ATG16L1 rs2241880.

Results: SHIP1 protein levels are profoundly diminished in a subset of patients; however, SHIP1 activity and expression are not correlated to ATG16L1 SNP status in this adult cohort.

Conclusions: Aberrant SHIP1 activity can contribute to disease in a subset of adult CD patients, and warrants further investigation.

MeSH terms

  • Adult
  • Autophagy-Related Proteins / genetics*
  • Cell Line
  • Cohort Studies
  • Crohn Disease / genetics*
  • Crohn Disease / metabolism
  • Down-Regulation*
  • Female
  • Gene Expression Regulation
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / genetics*
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / metabolism*
  • Polymorphism, Single Nucleotide*
  • Young Adult

Substances

  • ATG16L1 protein, human
  • Autophagy-Related Proteins
  • INPP5D protein, human
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases