| Autor: |
Hayet, Rafa, Sarra, Benkhelifa, Sonia, AitYounes, Houria, Saoula, Said, Belhadef, Mourad, Belkhelfa, Aziza, Boukercha, Ryma, Toumi, Imene, Soufli, Olivier, Moralès, Yvan, de Launoit, Hassen, Mahfouf, M'hamed, Nakmouche, Nadira, Delhem, Chafia, Touil-Boukoffa |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
Mediators of Inflammation |
| ISSN: |
1466-1861 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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