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KMID : 0363720060390060425
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Korean Journal of Anatomy
2006 Volume.39 No. 6 p.425 ~ p.432
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HO-1 Reduces the Severity of Trinitrobenzene Sulfonic Acid-induced Colitis through Suppression of NF-κB Activation
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Lee Seung-Pil
Song Jeong-Hoon
Jang Sung-Jo
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Abstract
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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-α), interleukin (IL)-1β 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-α, IL-1β and ICAM-1 induced by TNBS. Furthermore CoPPIX suppressed NF-κB 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-κB activity via induction of HO-1 during pathogenesis of TNBS-induced colitis.
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KEYWORD
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HO-1, TNF-α, TNBS, NF-κB, Colitis
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