Related Experiment Video
Updated: May 15, 2026

DNBS/TNBS Colitis Models: Providing Insights Into Inflammatory Bowel Disease and Effects of Dietary Fat
Published on: February 27, 2014
The unfolded protein response and chemical chaperones reduce protein misfolding and colitis in mice
Stewart Siyan Cao1, Ellen M Zimmermann, Brandy-Mengchieh Chuang
1Del E. Webb Neuroscience, Aging and Stem Cell Research Center, Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Background & Aims:
Endoplasmic reticulum (ER) stress has been associated with development of inflammatory bowel disease. We examined the effects of ER stress-induced chaperone response and the orally active chemical chaperones tauroursodeoxycholate (TUDCA) and 4-phenylbutyrate (PBA), which facilitate protein folding and reduce ER stress, in mice with colitis.
Methods:
We used dextran sulfate sodium (DSS) to induce colitis in mice that do not express the transcription factor ATF6α or the protein chaperone P58(IPK). We examined the effects of TUDCA and PBA in cultured intestinal epithelial cells (IECs); in wild-type, P58(IPK-/-), and Atf6α(-/-) mice with colitis; and in Il10(-/-) mice.
Results:
P58(IPK-/-) and Atf6α(-/-) mice developed more severe colitis following administration of DSS than wild-type mice. IECs from P58(IPK-/-) mice had excessive ER stress, and apoptotic signaling was activated in IECs from Atf6α(-/-) mice. Inflammatory stimuli induced ER stress signals in cultured IECs, which were reduced by incubation with TUDCA or PBA. Oral administration of either PBA or TUDCA reduced features of DSS-induced acute and chronic colitis in wild-type mice, the colitis that develops in Il10(-/-) mice, and DSS-induced colitis in P58(IPK-/-) and Atf6α(-/-) mice. Reduced signs of colonic inflammation in these mice were associated with significantly decreased ER stress in colonic epithelial cells.
Conclusions:
The unfolded protein response induces expression of genes that encode chaperones involved in ER protein folding; these factors prevent induction of colitis in mice. Chemical chaperones such as TUDCA and PBA alleviate different forms of colitis in mice and might be developed for treatment of inflammatory bowel diseases.
Related Concept Videos
The Unfolded Protein Response
Molecular Chaperones and Protein Folding
The...
Molecular Chaperones and Protein Folding
The...
Regulation of the Unfolded Protein Response
Bacterial Protein Maturation
Protein Folding Quality Check in the RER
