| Title: |
All-Trans Retinoic Acid Modulates TLR4/NF- κ B Signaling Pathway Targeting TNF- α and Nitric Oxide Synthase 2 Expression in Colonic Mucosa during Ulcerative Colitis and Colitis Associated Cancer |
| Authors: |
Rafa, Hayet; Benkhelifa, Sarra; Aityounes, Sonia; Saoula, Houria; Belhadef, Said; Belkhelfa, Mourad; Boukercha, Aziza; Toumi, Ryma; Soufli, Imene; Morales, Olivier; de Launoit, Yvan; Mahfouf, Hassen; Nakmouche, M'Hamed; Delhem, Nadira; Touil-Boukoffa, Chafia |
| Contributors: |
Université des Sciences et de la Technologie Houari Boumediene = University of Sciences and Technology Houari Boumediene Alger (USTHB); Institut de biologie de Lille - IBL (IBLI); Université de Lille, Sciences et Technologies-Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS); Hôpital Maillot Algérie; Hôpital Rouïba Algerie; Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 (M3T); Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS); They thank the national agency of research development in health (ATRSS) and “Agence Universitaire de la Francophonie” which supported their project. They have also received support from the SIRIC ONCOLille.; The authors thank the technical and surgical staff of the Department of Gastroenterology (Maillot Hospital), Department of Oncology (Rouiba Hospital), and Anatomic Pathology Service (Mustapha Pacha Hospital) Algiers, Algeria, for providing blood and colonic biopsies. They thank all voluntary participants in this study. |
| Source: |
ISSN: 0962-9351. |
| Publisher Information: |
CCSD; Hindawi Publishing Corporation |
| Publication Year: |
2017 |
| Collection: |
LillOA (HAL Lille Open Archive, Université de Lille) |
| Subject Terms: |
MESH: Aged; MESH: Blotting; Western; MESH: Colitis/blood; MESH: Colitis; Ulcerative/blood; Ulcerative/metabolism; MESH: Colorectal Neoplasms/blood; MESH: Colorectal Neoplasms/metabolism; MESH: Enzyme-Linked Immunosorbent Assay; MESH: Female; MESH: Humans; MESH: Immunohistochemistry; MESH: Intestinal Mucosa/metabolism; MESH: Male; MESH: Middle Aged; MESH: Nitric Oxide/blood; MESH: Nitric Oxide Synthase Type II/metabolism; MESH: Real-Time Polymerase Chain Reaction; MESH: Tumor Necrosis Factor-alpha/blood; [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry; Molecular Biology/Genomics [q-bio.GN]; [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology; [SDV.CAN]Life Sciences [q-bio]/Cancer |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/28408791; PUBMED: 28408791; PUBMEDCENTRAL: PMC5376956 |
| DOI: |
10.1155/2017/7353252 |
| Availability: |
https://hal.science/hal-02391613; https://hal.science/hal-02391613v1/document; https://hal.science/hal-02391613v1/file/AllTrans_Retinoic_acid_modulates_TLR4NFB_signaling.pdf; https://doi.org/10.1155/2017/7353252 |
| Rights: |
http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.B4397637 |
| Database: |
BASE |