Heme Oxygenase-1 is Involved in the Down-regulation of Nuclear Transcription Factor kappa B Activation in the Colonic Epithelium During Inflammation.
- Author:
Ki Jung YUN
1
;
Yu Rim KIM
;
Heung Jae LEE
;
Kyoung Suk KIM
;
Young Mi KWON
;
Min Kyu CHOI
;
Jae Min OH
;
Yeun Tai CHUNG
Author Information
1. Department of Anatomy, School of Medicine, Wonkwang University, Korea. jmoh@wonkwang.ac.kr
- Publication Type:Original Article
- Keywords:
Cobalt protoporphyrin IX;
Heme oxygenase-1;
Nuclear transcription factor kappa B;
Trinitrobenzene sulfonic acid;
Colitis
- MeSH:
Animals;
Carbon Monoxide;
Cobalt;
Colitis;
Colon*;
Cytokines;
Down-Regulation*;
Epithelial Cells;
Epithelium*;
Heme Oxygenase-1*;
Heme*;
HT29 Cells;
Humans;
Inflammation*;
Inflammatory Bowel Diseases;
Interleukin-1beta;
Iron;
Metabolism;
Mice;
NF-kappa B;
Tissue Donors;
Transcription Factors*;
Tumor Necrosis Factor-alpha
- From:Korean Journal of Anatomy
2004;37(6):571-577
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with anti-inflammatory activity, but the mechanisms underlying this activity are incompletely understood. Nuclear transcription factor kappa B (NF-kappa B) activation is an important factor in the pathogenesis of inflammatory bowel disease (IBD). We investigated the suppressive effects of HO-1 on the activation of NF-kappa B by pro-inflammatory cytokines in cultured colonic epithelial cells and by trinitrobenzene sulfonic acid (TNBS) in the colon of mice. The expression level of HO-1 in the colonic epithelium of a patient with inflammatory bowel disease and pseudo-membranous colitis was lower than that in a healthy control subject. In cultured human colonic epithelial HT-29 cells, pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha ) and IL-1 beta down-regulate HO-1 expression. The HO-1 inducer, cobalt protoporphyrin IX (CoPPIX), dramatically down-regulated NF-kappa B activation in HT-29 cells by TNF-alpha. In addition, bilirubin-a product of heme catabolism by HO-1-and the carbon monoxide donor tricarbonyldichlororuthenium (II) dimer also suppressed NF-kappa B activation by TNF-alpha. However, iron, another heme metabolite, did not suppress NF-kappa B activation by TNF-alpha. Furthermore, CoPPIX diminished the macroscopic and histopathological symptoms of TNBS-induced colitis and down-regulated NF-kappa B activation in mice. In conclusion, this study suggests that HO-1 plays an important role in the down-regulation of NF-kappa B activation, which is a key factor in the pathogenesis of IBD and is thus an excellent therapeutic target for the treatment of IBD.
