Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2018 May 15;23(7):1962–1976. doi: 10.1016/j.celrep.2018.04.053

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© 2018 The Author(s)

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

PMC Copyright notice

Enterocyte Self-Regulation of NO Levels Is the Most Beneficial Treatment for Colitis

Colitis was induced in C57BL/6J.OlaHsd mice with DSS for 6 days, followed by administration of either intraperitoneal (i.p.) fisetin, citrulline solution in drinking water, a combination of both treatments, or only DMSO as a control; the experiment was repeated 3 times.

(A) FACS analysis of colon epithelial cells from mice treated with the combined treatment shows a significant increase in NO levels compared with the control group (n = 4 in each group).

(B) A significant weight loss is documented in the control group compared with the treated mice (n ≥ 20 in each group).

(C) An endoscopic evaluation demonstrates a significant improvement on day 12 in the colitis score of the treated groups compared with the control. Among the treatments, the combined treatment was the most beneficial (n ≥ 20 in each group).

(D) A significant longer colon length is seen in the treated groups compared with the control. In addition, the colon is significantly longer with combined treatment compared with each treatment separately (n = 15 in both groups).

(E) A significant reduction in histological score in all treatment groups compared with the control.

(F and G) Colitis was induced by bone marrow (BM) implantation from either WT or CX₃CR1^Cre:Il10ra^fl/fl donors to lethally irradiated Asl^f/f mice. Two weeks after transplantation, mice were treated with a combination of citrulline and fisetin and compared with control animals treated with DMSO only. Colitis severity was evaluated 6 weeks after the implantation.

(F) No colitis signs were observed in animals implanted with WT donor BM. In animals implanted with CX₃CR1^Cre:Il10ra^fl/fl BM, a significant reduction in colitis severity was seen in treated animals compared with control mice, as shown by reduced weight loss (top left), a reduced colitis score (top right), increased colon length (bottom left), and a reduced histology score (bottom right) (n > 5 in each group, experiments were repeated twice).

(G) In vivo intestinal permeability assay to assess epithelial barrier function, performed using FITC-labeled dextran, showing significantly decreased permeability in treated mice compared with controls.

(H) Caco-2 cells plotted for resistance percentage over time, showing a significant decrease in conductivity of the control group compared with the group treated with citrulline and fisetin (the experiment included at least 5 biological repetitions).

Error bars represent SEM.