J Korean Med Sci.  2018 Mar;33(13):e110. 10.3346/jkms.2018.33.e110.

Up-regulation of IGF Binding Protein-3 Inhibits Colonic Inflammatory Response

• Kim SC
• Hwang PH

• KMID: 2409215
• DOI: http://doi.org/10.3346/jkms.2018.33.e110

Abstract

BACKGROUND
The aggravating factors still remained unclear in inflammatory bowel disease (IBD). Despite many different therapeutic approaches, many patients do not respond to the therapy. The anti-inflammatory effect of insulin-like growth factor-binding protein-3 (IGFBP-3) was suggested because of its capability of nuclear factor-κB (NF-κB) signaling inhibition. Therefore, we hypothesized that the up-regulation of IGFBP-3 would inhibit an inflammatory process.
METHODS
Lipopolysaccharides (LPS) treated intestinal epithelial cell 6 (IEC-6) and dextran sodium sulfate (DSS) induced colitis mice were used as colitis models. Exogenous IGFBP-3 expression was accomplished using the adenoviral vector system expressing IGFBP-3 (Ad/IGFBP-3). The inflammatory responses and relevant cellular responses in IEC-6 cells influenced by IGFBP-3 expression were evaluated by western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and reactive oxygen species (ROS) measurement. The severity of colitis was evaluated with the colon tissues of DSS-induced mouse model.
RESULTS
We found that the IGFBP-3 expression reduced the production of inflammatory cytokines (cyclooxygenase-2, interleukin-1β, tumor necrosis factor-α) and ROS formation. IGFBP-3 expression also induced cell viability and inhibited NF-κB activation. In line with this data, the severity of DSS-induced mouse colitis was greatly ameliorated by the treatment of IGFBP-3 expressing adenoviral particles characterized with less weight loss and preserved colon length compared with the mice treated with DSS alone. The histopathology of the colon showed the reducing signs of colitis in Ad/IGFBP-3 treated DSS-mice group.
CONCLUSION
Therefore, our data suggest that Ad/IGFBP-3 up-regulation reduces colonic inflammatory response as a novel therapeutic protocol for IBD.

Keyword

Colitis; COX-2; IEC-6; NF-κB; TNF-α

MeSH Terms

Animals
Blotting, Western
Cell Survival
Colitis
Colon*
Cytokines
Dextrans
Epithelial Cells
Humans
Inflammatory Bowel Diseases
Insulin-Like Growth Factor Binding Protein 3
Lipopolysaccharides
Mice
Necrosis
Reactive Oxygen Species
Sodium
Up-Regulation*
Weight Loss
Cytokines
Dextrans
Insulin-Like Growth Factor Binding Protein 3
Lipopolysaccharides
Reactive Oxygen Species
Sodium