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Role of tristetraprolin phosphorylation in paediatric patients with inflammatory bowel disease.

Authors
  • Di Silvestre, Alessia1
  • Lucafò, Marianna2
  • Pugnetti, Letizia1
  • Bramuzzo, Matteo2
  • Stocco, Gabriele3
  • Barbi, Egidio2
  • Decorti, Giuliana4
  • 1 PhD School in Science of Reproduction and Development, University of Trieste, Trieste 34127, Italy. , (Italy)
  • 2 Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste 34137, Italy. , (Italy)
  • 3 Department of Life Sciences, University of Trieste, Trieste 34127, Italy. , (Italy)
  • 4 Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste 34137, Italy. [email protected] , (Italy)
Type
Published Article
Journal
World journal of gastroenterology
Publication Date
Oct 21, 2019
Volume
25
Issue
39
Pages
5918–5925
Identifiers
DOI: 10.3748/wjg.v25.i39.5918
PMID: 31660029
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Intestinal inflammation and epithelial injury are the leading actors of inflammatory bowel disease (IBD), causing an excessive pro-inflammatory cytokines expression. Tristetraprolin (TTP), an mRNA binding protein, plays a role in regulating the inflammatory factors, recognizing specific sequences on the 3' untranslated region of cytokine mRNAs. TTP activity depends on its phosphorylation state: the unphosphorylated TTP degrades pro-inflammatory cytokine mRNAs; on the contrary, the phosphorylated TTP fails to destabilize mRNAs furthering their expression. The phospho-TTP forms a complex with the chaperone protein 14-3-3. This binding could be one of the factors that promote intestinal inflammation as a cause of disease progression. To assess if TTP phosphorylation has a role in paediatric IBD. The study was carried out on a cohort of paediatric IBD patients. For each patient enrolled, a specimen of inflamed and non-inflamed colonic mucosa was collected. Furthermore, the experiments were conducted on macrophages differentiated from blood samples of the same patients. Macrophages from healthy donors' blood were used as controls. Co-immunoprecipitation assay and immunoblotting analyses were performed to observe the formation of the phospho-TTP/14-3-3 complex. In the same samples TNF-α expression was also evaluated as major factor of the pro-inflammatory activity. In this work we studied indirectly the phosphorylation of TTP through the binding with the chaperone protein 14-3-3. In inflamed and non-inflamed colon mucosa of IBD paediatric patients immunoblot assay demonstrated a higher expression of the TTP in inflamed samples respect to the non-inflamed; the co-immunoprecipitated 14-3-3 protein showed the same trend of expression. In the TNF-α gene expression analysis higher levels of the cytokine in inflamed tissues compared to controls were evident. The same experiments were conducted on macrophages from IBD paediatric patients and healthy controls. The immunoblot results demonstrated a high expression of both TTP and co-immunoprecipitated 14-4-3 protein in IBD-derived macrophages in comparison to healthy donors. TNF-α protein levels from macrophages lysates showed the same trend of expression in favour of IBD paediatric patients compared to healthy controls. In this work, for the first time, we describe a relation between phospho-TTP/14-3-3 complex and IBD. Indeed, a higher expression of TTP/14-3-3 was recorded in IBD samples in comparison to controls. ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.

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