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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2020

01-12-2020 | Celiac Disease | Research

Role of IL-24 in the mucosal remodeling of children with coeliac disease

Authors: Réka Rokonay, Apor Veres-Székely, Beáta Szebeni, Domonkos Pap, Rita Lippai, Nóra J. Béres, Gábor Veres, Attila J. Szabó, Ádám Vannay

Published in: Journal of Translational Medicine | Issue 1/2020

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Abstract

Background

Recently, involvement of IL-19, IL-20 and IL-24 has been reported in inflammatory diseases associated with tissue remodeling. However, their impact on the pathomechanism of coeliac disease (CD) is still completely unknown.

Methods

Expression of IL19, IL20 and IL24 was measured by real-time RT-PCR, protein amount of IL-24, α smooth muscle actin (α-SMA) and fibronectin (FN) was determined by Western-blot analysis in the duodenal biopsies of therapy naive children with CD and controls. Localization of IL-24 and IL-20RB was investigated by immunofluorescent staining in the duodenal mucosa. Effect of recombinant IL-1β, TNF-α, TGF-β and IL-17 treatment on the expression of IL19, IL20, IL24 and their receptors was investigated by real-time RT-PCR in small intestinal epithelial cells (FHs74Int), in primary duodenal myofibroblasts (pdMFs) and in peripheral blood mononuclear cells (PBMCs). Effect of IL-24 on H2O2 treated FHs74Int cells and on pdMFs was measured by MTT, LDH, Annexin V assays, real-time RT-PCR and by fluorescent microscopy.

Results

We found increased level of IL-24 (3.3×, p < 0.05), α-SMA (2.4×, p < 0.05) and FN (2.3×, p < 0.05) in the duodenal mucosa and increased expression of IL19 (3.6×, p < 0.05) and IL24 (5.2×, p < 0.05) in the PBMCs of children with CD compared to that of controls. IL-1β was a strong inducer of IL24 expression of FHs74Int cells (9.9×, p < 0.05), pdMFs (552.9×, p < 0.05) or PBMCs (17.2×, p < 0.05), as well. IL-24 treatment reduced the number of apoptotic cells (0.5×, p < 0.05) and decreased the expression of inflammatory factors, including IL1A, IL6 and TNF of H2O2-treated FHs74Int cells. IL-24 decreased the proliferation (0.6×, p < 0.05) of PDGF-B treated pdMFs. Moreover, IL-24 treatment altered the morphology of pdMFs by influencing the size of the angles between stress fibers and the longitudinal axis of the cells (2.0×, p < 0.05) and the expression of cytoskeletal components, including ACTA2, ACTB, VIM, SNAI1 and SNAI2.

Conclusion

Our results suggest that IL-24 plays a significant role in the maintenance of duodenal mucosal integrity in CD.
Appendix
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Metadata
Title
Role of IL-24 in the mucosal remodeling of children with coeliac disease
Authors
Réka Rokonay
Apor Veres-Székely
Beáta Szebeni
Domonkos Pap
Rita Lippai
Nóra J. Béres
Gábor Veres
Attila J. Szabó
Ádám Vannay
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2020
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-020-02221-2

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