Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2019; 25(39): 5918-5925
Published online Oct 21, 2019. doi: 10.3748/wjg.v25.i39.5918
Role of tristetraprolin phosphorylation in paediatric patients with inflammatory bowel disease
Alessia Di Silvestre, Marianna Lucafò, Letizia Pugnetti, Matteo Bramuzzo, Gabriele Stocco, Egidio Barbi, Giuliana Decorti
Alessia Di Silvestre, Letizia Pugnetti, PhD School in Science of Reproduction and Development, University of Trieste, Trieste 34127, Italy
Marianna Lucafò, Matteo Bramuzzo, Egidio Barbi, Giuliana Decorti, Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste 34137, Italy
Gabriele Stocco, Department of Life Sciences, University of Trieste, Trieste 34127, Italy
Egidio Barbi, Giuliana Decorti, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste 34127, Italy
Author contributions: Di Silvestre A and Decorti G contributed to the conception and design of the study; Di Silvestre A and Pugnetti L collected the data; Di Silvestre A, Lucafò M, Bramuzzo M performed data analysis and interpretation; Di Silvestre A drafted the article; Lucafò M, Stocco G, Barbi E and Decorti G critically reviewed the article.
Supported by the Italian Ministry of Health projects Ricerca Corrente 1/17 and 21/17 (Institute for Maternal and Child Health IRCCS Burlo Garofolo).
Institutional review board statement: The study was reviewed and approved by the Ethical Committee of the Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste, Italy.
Conflict-of-interest statement: The authors declare no competing financial, personal or professional conflicts of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The ARRIVE guidelines have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Giuliana Decorti, MD, Full Professor, Department of Medical, Surgical and Health Sciences, University of Trieste, Institute for Maternal and Child Health-IRCCS “Burlo Garofolo”, Via A. Fleming 22, Trieste, I-34127, Italy. decorti@units.it
Telephone: +39-40-5588777
Received: August 1, 2019
Peer-review started: August 1, 2019
First decision: August 27, 2019
Revised: September 6, 2019
Accepted: September 27, 2019
Article in press: September 27, 2019
Published online: October 21, 2019
Processing time: 80 Days and 20.4 Hours
ARTICLE HIGHLIGHTS
Research background

Inflammatory bowel disease (IBD) is an immune-mediated condition of the gastrointestinal tract characterized by chronic, relapsing or progressive inflammatory condition. Tristetraprolin (TTP) is a zinc finger protein belonging to the group of mRNA-binding proteins. TTP is able to interact with pro-inflammatory cytokines mRNAs, influencing their stability. The function of TTP is affected by a post-translational modification. The unphosphorylated TTP destabilizes pro-inflammatory cytokines mRNAs; on the contrary, the phosphorylation of TTP impairs protein activity.

Research motivation

The incidence of paediatric IBD is increasing, and an optimal treatment is far from being achieved. Studies are therefore needed to enlighten new mechanisms that can be targeted by novel therapies.

Research objectives

The aim of this project is to assess if TTP phosphorylation has a role in paediatric IBD.

Research methods

A small cohort of IBD paediatric patients was enrolled for the study. For each patient, during a colonoscopy, inflamed and non-inflamed tissues were collected. Moreover, macrophages from the same patients and healthy donors were isolated. Co-immunoprecipitation assay and immunoblotting analyses were performed to evaluate the formation of the phospho-TTP/14-3-3 complex. TNF-α expression was also evaluated.

Research results

TTP and 14-3-3 protein expression was higher in inflamed colonic samples in comparison to the non-inflamed. Furthermore, TNF-α gene expression analysis showed the same pattern of expression. The protein analysis of TTP, co-immunoprecipitated 14-4-3 protein and TNF-α in macrophages of IBD patients and healthy donors demonstrated a higher expression of all the proteins in paediatric patients in comparison to controls.

Research conclusions

These data demonstrated for the first time a role of TTP in IBD inflammation. Indeed, TTP is highly expressed in both inflamed colon tissues and in macrophages of IBD patients.

Research perspectives

These preliminary results provide new information about the role of TTP in IBD, opening new perspectives in the investigation of a target therapy based on the modulation of TTP phosphorylation.