In:
Mediators of Inflammation, Hindawi Limited, Vol. 2017 ( 2017), p. 1-16
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0962-9351
,
1466-1861
DOI:
10.1155/2017/7353252
Sprache:
Englisch
Verlag:
Hindawi Limited
Publikationsdatum:
2017
ZDB Id:
2008065-7