Altered pattern of tumor necrosis factor-Alpha production in peripheral blood monocytes from Crohn's disease basic study

Claudia Loganes, Alessia Pin, Samuele Naviglio, Martina Girardelli, Anna Monica Bianco, Stefano Martelossi, Alberto Tommasini, Elisa Piscianz

Research output: Contribution to journalArticlepeer-review

Abstract

AIM To evaluate the inflammatory state in Crohn's disease (CD) patients and correlate it with genetic background and microbial spreading. METHODS By means of flow cytometry, production of tumor necrosis factor-Alpha (TNF-α) was measured in peripheral blood monocytes from patients suffering from CD, ulcerative colitis (UC) and in healthy subjects after stimulation of the NOD2 and TLR pathways. CD patients were genotyped for the three most common NOD2 variants (R702W, G908R and L1007Pfs∗2) and basal production of TNF-α was correlated to NOD2 genotype. Also, production of TNF-α was correlated to plasmatic levels of LPS Binding Protein (LBP), soluble (s) CD14 and to the activity state of the disease. RESULTS The patients with CD were characterized by a significantly higher monocyte basal expression of TNF-α compared with healthy subjects and UC patients, and after stimulation with Pam3CSK4 (ligand of TLR2/1) and MDP-L18 (ligand of NOD2) this difference was maintained, while other microbial stimuli (LPS, ligand of TLR4 and PolyI:C, ligand of TLR3) induced massive activation in CD monocytes as well as in UC and in healthy control cells. There was no significant difference in the production of TNF-α between patients who carried CD-Associated heterozygous or homozygous variants in NOD2 and patients with wild type NOD2 genotype. Although serum LBP levels have been shown to correlate positively with the state of activity of the disease, TNF-α production did not show a clear correlation with either LBP or sCD14 levels in plasma. Moreover, no clear correlation was seen between TNF-α production and activity indices in either CD or UC. CONCLUSION Peripheral monocytes from CD express higher basal and stimulated TNF-α than controls, regardless of NOD2 genotype and without a clear correlation with disease activity.

Original languageEnglish
Pages (from-to)9117-9126
Number of pages10
JournalWorld Journal of Gastroenterology
Volume22
Issue number41
DOIs
Publication statusPublished - Nov 7 2016

Keywords

  • Activity index
  • Crohn's disease
  • Dysbiosis
  • Lps-binding protein
  • Nod2 variants
  • Toll like receptors
  • Tumor necrosis factor-A
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology

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