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Mediators of Inflammation
Volume 2017 (2017), Article ID 7353252, 16 pages
Research Article

All-Trans Retinoic Acid Modulates TLR4/NF-κB Signaling Pathway Targeting TNF-α and Nitric Oxide Synthase 2 Expression in Colonic Mucosa during Ulcerative Colitis and Colitis Associated Cancer

1Team: Cytokines and NO Synthases-Immunity and Pathogenesis, Laboratory of Cellular and Molecular Biology (LBCM), Faculty of Biological Science, University of Sciences and Technology (USTHB), Algiers, Algeria
2Institut de Biologie de Lille, UMR 8161, CNRS, Institut Pasteur de Lille, Université Lille-Nord de France, Lille, France
3Anatomic Pathology Service, Mustapha Pacha Hospital, Algiers, Algeria
4Department of Gastroenterology, Maillot Hospital, Algiers, Algeria
5Service of Oncology, Rouiba Hospital, Algiers, Algeria

Correspondence should be addressed to Nadira Delhem and Chafia Touil-Boukoffa

Received 5 November 2016; Revised 5 January 2017; Accepted 19 February 2017; Published 20 March 2017

Academic Editor: Kumar S. Bishnupuri

Copyright © 2017 Hayet Rafa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Colitis associated cancer (CAC) is the colorectal cancer (CRC) subtype that is associated with bowel disease such as ulcerative colitis (UC). The data on role of NF-κB signaling in development and progression of CAC were derived from preclinical studies, whereas data from human are rare. The aim of this work was to study the contribution of NF-κB pathway during UC and CAC, as well as the immunomodulatory effect of all-trans retinoic acid (AtRA). We analyzed the expression of NOS2, TNF-α, TLR4, and NF-κB, in colonic mucosa. We also studied NO/TNF-α modulation by LPS in colonic mucosa pretreated with AtRA. A marked increase in TLR4, NF-κB, TNF-α, and NOS2 expression was reported in colonic mucosa. The relationship between LPS/TLR4 and TNF-α/NO production, as well as the role of NF-κB signaling, was confirmed by ex vivo experiments and the role of LPS/TLR4 in NOS2/TNF-α induction through NF-κB pathway was suggested. AtRA downregulates NOS2 and TNF-α expression. Collectively, our study indicates that AtRA modulates in situ LPS/TLR4/NF-κB signaling pathway targeting NOS2 and TNF-α expression. Therefore, we suggest that AtRA has a potential value in new strategies to improve the current therapy, as well as in the clinical prevention of CAC development and progression.