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The role of interleukin 17 in Crohn's disease-associated intestinal fibrosis

The role of interleukin 17 in Crohn's disease-associated intestinal fibrosis
The role of interleukin 17 in Crohn's disease-associated intestinal fibrosis
Background: Interleukin (IL)-17A and IL-17E (also known as IL-25) have been implicated in fibrosis in various tissues. However, the role of these cytokines in the development of intestinal strictures in Crohn's disease (CD) has not been explored. We investigated the levels of IL-17A and IL-17E and their receptors in CD strictured and non-strictured gut, and the effects of IL-17A and IL-17E on CD myofibroblasts.

Results: IL-17A was significantly overexpressed in strictured compared with non-strictured CD tissues, whereas no significant difference was found in the expression of IL-17E or IL-17A and IL-17E receptors (IL-17RC and IL-17RB, respectively) in strictured and non-strictured CD areas. Strictured CD explants released significantly higher amounts of IL-17A than non-strictured explants, whereas no difference was found as for IL-17E, IL-6, or tumor necrosis factor-? production. IL-17A, but not IL-17E, significantly inhibited myofibroblast migration, and also significantly upregulated matrix metalloproteinase (MMP)-3, MMP-12, tissue inhibitor of metalloproteinase-1 and collagen production by myofibroblasts from strictured CD tissues.

Conclusions: Our results suggest that IL-17A, but not IL-17E, is pro-fibrotic in CD. Further studies are needed to clarify whether the therapeutic blockade of IL-17A through the anti-IL-17A monoclonal antibody secukinumab is able to counteract the fibrogenic process in CD.
collagen, interleukin 25, myofibroblast, stricture, TIMP-1
Biancheri, Paolo
479c256d-187d-4b65-b226-8069299e61b2
Pender, Sylvia L.F.
62528b03-ec42-41bb-80fe-48454c2c5242
Ammoscato, Francesca
7cba8af5-d727-4d3f-bbca-49cc4bae809f
Giuffrida, Paolo
7089a195-db88-4489-8c00-638a9cc61fd5
Sampietro, Gianluca
9cb656a0-4ba8-49d4-9fb3-5cfb026090e2
Ardizzone, Sandro
5b10ad7b-a7d1-435f-af14-8a01d4fe8492
Ghanbari, Amir
759ff551-c177-41ba-9b12-e9a883cc21dd
Curciarello, Renata
8ae1c234-3f01-41c0-8cff-a02dd96b6037
Pasini, Alessandra
06c34153-b02d-4d2d-98eb-58350259775d
Monteleone, Giovanni
a289342b-54b5-414a-9e06-aa6b052f91b2
Corazza, Gino R.
629c0861-c13c-4ae9-ad41-0cc3c1309857
Macdonald, Thomas T.
a6bde8a9-acc4-4128-851f-dd5dbfe28816
Di Sabatino, Antonio
08cb3ec3-e4a0-423c-aa27-f428979b957d
Biancheri, Paolo
479c256d-187d-4b65-b226-8069299e61b2
Pender, Sylvia L.F.
62528b03-ec42-41bb-80fe-48454c2c5242
Ammoscato, Francesca
7cba8af5-d727-4d3f-bbca-49cc4bae809f
Giuffrida, Paolo
7089a195-db88-4489-8c00-638a9cc61fd5
Sampietro, Gianluca
9cb656a0-4ba8-49d4-9fb3-5cfb026090e2
Ardizzone, Sandro
5b10ad7b-a7d1-435f-af14-8a01d4fe8492
Ghanbari, Amir
759ff551-c177-41ba-9b12-e9a883cc21dd
Curciarello, Renata
8ae1c234-3f01-41c0-8cff-a02dd96b6037
Pasini, Alessandra
06c34153-b02d-4d2d-98eb-58350259775d
Monteleone, Giovanni
a289342b-54b5-414a-9e06-aa6b052f91b2
Corazza, Gino R.
629c0861-c13c-4ae9-ad41-0cc3c1309857
Macdonald, Thomas T.
a6bde8a9-acc4-4128-851f-dd5dbfe28816
Di Sabatino, Antonio
08cb3ec3-e4a0-423c-aa27-f428979b957d

Biancheri, Paolo, Pender, Sylvia L.F., Ammoscato, Francesca, Giuffrida, Paolo, Sampietro, Gianluca, Ardizzone, Sandro, Ghanbari, Amir, Curciarello, Renata, Pasini, Alessandra, Monteleone, Giovanni, Corazza, Gino R., Macdonald, Thomas T. and Di Sabatino, Antonio (2013) The role of interleukin 17 in Crohn's disease-associated intestinal fibrosis. Fibrogenesis & Tissue Repair, 6. (doi:10.1186/1755-1536-6-13). (PMID:23834907)

Record type: Article

Abstract

Background: Interleukin (IL)-17A and IL-17E (also known as IL-25) have been implicated in fibrosis in various tissues. However, the role of these cytokines in the development of intestinal strictures in Crohn's disease (CD) has not been explored. We investigated the levels of IL-17A and IL-17E and their receptors in CD strictured and non-strictured gut, and the effects of IL-17A and IL-17E on CD myofibroblasts.

Results: IL-17A was significantly overexpressed in strictured compared with non-strictured CD tissues, whereas no significant difference was found in the expression of IL-17E or IL-17A and IL-17E receptors (IL-17RC and IL-17RB, respectively) in strictured and non-strictured CD areas. Strictured CD explants released significantly higher amounts of IL-17A than non-strictured explants, whereas no difference was found as for IL-17E, IL-6, or tumor necrosis factor-? production. IL-17A, but not IL-17E, significantly inhibited myofibroblast migration, and also significantly upregulated matrix metalloproteinase (MMP)-3, MMP-12, tissue inhibitor of metalloproteinase-1 and collagen production by myofibroblasts from strictured CD tissues.

Conclusions: Our results suggest that IL-17A, but not IL-17E, is pro-fibrotic in CD. Further studies are needed to clarify whether the therapeutic blockade of IL-17A through the anti-IL-17A monoclonal antibody secukinumab is able to counteract the fibrogenic process in CD.

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More information

Published date: 8 July 2013
Additional Information: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: collagen, interleukin 25, myofibroblast, stricture, TIMP-1
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 356138
URI: https://eprints.soton.ac.uk/id/eprint/356138
PURE UUID: a8ec074c-b282-4b0f-a002-84b563dd9a07
ORCID for Sylvia L.F. Pender: ORCID iD orcid.org/0000-0001-6332-0333

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Date deposited: 11 Sep 2013 10:25
Last modified: 06 Jun 2018 12:51

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Contributors

Author: Paolo Biancheri
Author: Francesca Ammoscato
Author: Paolo Giuffrida
Author: Gianluca Sampietro
Author: Sandro Ardizzone
Author: Amir Ghanbari
Author: Renata Curciarello
Author: Alessandra Pasini
Author: Giovanni Monteleone
Author: Gino R. Corazza
Author: Thomas T. Macdonald
Author: Antonio Di Sabatino

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