HO-1 Mediates Intracellular Calcium Modulation and Inhibits TNF-alpha-induced NF-kappaB Activity in Human Colonic Epithelial Cell Line / 대한해부학회지
Korean Journal of Anatomy
;
: 401-406, 2006.
Article
in English
| WPRIM
| ID: wpr-643795
ABSTRACT
Heme oxygenage-1 (HO-1) is the rate-limiting enzyme in heme catabolism, which leads to the generation of carbon monoxide (CO), biliverdin, and free iron. HO-1 has been known to show strong immunosuppressive properties although its mechanisms are not completely understood. In this study, it was therefore investigated anti-inflammatory properties of HO-1 in HT-29 cell, human colonic epithelial cell line. CoPPIX, HO-1 inducer, induced HO-1 expression without NF-kappa B activation and significantly blocked the I kappa B-alpha degradation by TNF-alpha in HT-29. Inhibition of HO-1 activity by ZnPPIX reversed the suppressive effects of CoPPIX on I kappa B-alpha degradation by TNF-alpha. Calcium chelating agent BAPTA/AM and calcium channel blockers, Verapamil and Flunarizine suppressed I kappa B-alpha degradation by TNF-alpha in HT-29 cells like CoPPIX while calcium ionophore A23187 also dose-dependently reversed the suppressive effects of CoPPIX on I kappa B-alpha degradation by TNF-alpha like a ZnPPIX. Interestingly, treatment of ZnPPIX increased basal intracellular calcium in HT-29 cells. Collectively, these results suggest that HO-1 exerts anti-inflammatory effects by down-regulation of NF-kappa B activity via suppression of intracellular calcium during pathogenesis of colitis in colonic epithelium.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Biliverdine
/
Carbon Monoxide
/
Calcium Channel Blockers
/
Flunarizine
/
Verapamil
/
Down-Regulation
/
Calcium
/
NF-kappa B
/
Calcimycin
/
Tumor Necrosis Factor-alpha
Limits:
Humans
Language:
English
Journal:
Korean Journal of Anatomy
Year:
2006
Type:
Article
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