Korean J Anat.  2006 Dec;39(6):425-432.

HO-1 Reduces the Severity of Trinitrobenzene Sulfonic Acid-induced Colitis through Suppression of NF-kappaB Activation

Affiliations
  • 1Department of Obstetrics and Gynecology, Wonkwang University School of Medicine and Wonkwang Medical Science Institute, Iksan, Chonbuk, Korea.
  • 2Department of Plastic and Reconstructive Surgery, Wonkwang University School of Medicine and Wonkwang Medical Science Institute, Iksan, Chonbuk, Korea.
  • 3Department of Neurosurgery, Wonkwang University School of Medicine and Wonkwang Medical Science Institute, Iksan, Chonbuk, Korea. jang4025@wonkwang.ac.kr

Abstract

Heme oxygenage-1 (HO-1), rate-limiting enzyme in heme catabolism, has been known to show strong immune-suppressive properties although its mechanisms are not completely understood. In this study, the authors investigated the mechanism whereby HO-1 has anti-inflammatory properties in trinitrobenzene sulfonic acid (TNBS)-induced colitis. Body weight was evaluated and tumor necrosis factor (TNF-alpha), interleukin (IL)-1beta and intercellular adhesion molecule-1 (ICAM-1) were detected by immunohistochemical staining. Heme oxygenase-1 (HO-1) expression was analyzed by Western blot and immunohistochemical staining. In a mouse model, HO-1 inducer, cobalt-protoporphyrin IX (CoPPIX) administration significantly improved the clinical symptoms and histopathologic changes of trinitrobenzene sulfonic acid (TNBS) colitis as well as significantly suppressed the expression of several inflammatory mediators such as TNF-alpha, IL-1beta and ICAM-1 induced by TNBS. Furthermore CoPPIX suppressed NF-kappaB activation that is an important transcription factor for expression of proinflammatory mediators in TNBS colitis while HO-1 activity inhibitor, zinc protoporphyrin IX (ZnPPIX) reversed the protective effects of CoPPIX in TNBS colitis. Collectively, these results suggest that HO-1 exerts anti-inflammatory effects by down-regulation of NF-kappaB activity via induction of HO-1 during pathogenesis of TNBS-induced colitis.

Keyword

HO-1; TNF-alpha; TNBS; NF-kappaB; Colitis

MeSH Terms

Animals
Blotting, Western
Body Weight
Colitis*
Down-Regulation
Heme
Heme Oxygenase-1
Intercellular Adhesion Molecule-1
Interleukins
Metabolism
Mice
NF-kappa B*
Transcription Factors
Tumor Necrosis Factor-alpha
Zinc
Heme
Heme Oxygenase-1
Intercellular Adhesion Molecule-1
Interleukins
NF-kappa B
Transcription Factors
Tumor Necrosis Factor-alpha
Zinc
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