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. (20th March 2017)

• Record Type: Journal Article
• Authors: Rafa, Hayet; Benkhelifa, Sarra; AitYounes, Sonia; Saoula, Houria; Belhadef, Said; Belkhelfa, Mourad; Boukercha, Aziza; Toumi, Ryma; Soufli, Imene; Moralès, Olivier; de Launoit, Yvan; Mahfouf, Hassen; Nakmouche, M'hamed; Delhem, Nadira; Touil-Boukoffa, Chafia
• Other Names: Bishnupuri Kumar S. Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2017(2017)
• Publication Date: 2017-03-20
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2017/7353252
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : 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- κ B 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- κ B 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- κ B, in colonic mucosa. We also studied NO/TNF- α modulation by LPS in colonic mucosa pretreated with AtRA. A marked increase in TLR4, NF- κ B, 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- κ B signaling, was confirmed by ex vivo experiments and the role of LPS/TLR4 in NOS2/TNF- α induction through NF- κ B pathway was suggested. AtRA downregulates NOS2 and TNF- α expression. Collectively, our study indicates that AtRA modulates in situ LPS/TLR4/NF- κ B 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.