Heme Oxygenase-1 is Involved in the Down-regulation of Nuclear Transcription Factor kappa B Activation in the Colonic Epithelium During Inflammation / 대한해부학회지
Korean Journal of Anatomy
;
: 571-577, 2004.
Artículo
en Coreano
| WPRIM
| ID: wpr-646406
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.
Texto completo:
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Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Donantes de Tejidos
/
Factores de Transcripción
/
Monóxido de Carbono
/
Enfermedades Inflamatorias del Intestino
/
Regulación hacia Abajo
/
Citocinas
/
FN-kappa B
/
Factor de Necrosis Tumoral alfa
/
Cobalto
/
Colitis
Límite:
Animales
/
Humanos
Idioma:
Coreano
Revista:
Korean Journal of Anatomy
Año:
2004
Tipo del documento:
Artículo
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