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

被引：97

作者：

Rafa, Hayet ^{[1
,2
]}

Benkhelifa, Sarra ^{[1
,2
]}

AitYounes, Sonia ^{[3
]}

Saoula, Houria ^{[4
]}

Belhadef, Said ^{[5
]}

Belkhelfa, Mourad ^{[1
]}

Boukercha, Aziza ^{[1
]}

Toumi, Ryma ^{[1
]}

Soufli, Imene ^{[1
]}

Morales, Olivier ^{[2
]}

de launoit, Yvan ^{[2
]}

Mahfouf, Hassen ^{[5
]}

Nakmouche, M'hamed ^{[4
]}

Delhem, Nadira ^{[2
]}

Touil-Boukoffa, Chafia ^{[1
]}

机构：

[1] Univ Sci & Technol USTHB, Fac Biol Sci, Lab Cellular & Mol Biol LBCM, Team Cytokines & Synth Immun & Pathogenesis, Algiers, Algeria

[2] Univ Lille Nord France, Inst Pasteur Lille, CNRS, Inst Biol Lille,UMR 8161, Lille, France

[3] Mustapha Pacha Hosp, Anat Pathol Serv, Algiers, Algeria

[4] Maillot Hosp, Dept Gastroenterol, Algiers, Algeria

[5] Rouiba Hosp, Serv Oncol, Algiers, Algeria

来源：

MEDIATORS OF INFLAMMATION | 2017年 / 2017卷

关键词：

NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA; COLORECTAL-CANCER; RECEPTOR-BETA; X-RECEPTOR; T-CELL; GROWTH; TLR4;

D O I：

10.1155/2017/7353252

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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-kappa 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-kappa 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-alpha, TLR4, and NF-kappa B, in colonic mucosa. We also studied NO/TNF-alpha modulation by LPS in colonic mucosa pretreated with AtRA. A marked increase in TLR4, NF-kappa B, TNF-alpha, and NOS2 expression was reported in colonic mucosa. The relationship between LPS/TLR4 and TNF-alpha/NO production, as well as the role of NF-kappa B signaling, was confirmed by ex vivo experiments and the role of LPS/TLR4 in NOS2/TNF- alpha induction through NF-kappa B pathway was suggested. AtRA downregulates NOS2 and TNF-alpha expression. Collectively, our study indicates that AtRA modulates in situ LPS/TLR4/NF-kappa B signaling pathway targeting NOS2 and TNF-alpha 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.

引用

页数：16

共 99 条

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TLR4 and MD-2 expression is regulated by immune-mediated signals in human intestinal epithelial cells [J].