HO-1 Mediates Intracellular Calcium Modulation and Inhibits TNF-alpha-induced NF-kappaB Activity in Human Colonic Epithelial Cell Line.
- Author:
Yu Rim KIM
1
;
Sung Jo JANG
Author Information
1. Department of Anatomy, Wonkwang University School of Medicine and Wonkwang Medical Science Institute, Iksan, Chonbuk, Korea. jang4025@wonkwang.ac.kr
- Publication Type:Original Article
- Keywords:
HO-1;
NF-kappa B;
Intracellular calcium;
HT-29
- MeSH:
Biliverdine;
Calcimycin;
Calcium Channel Blockers;
Calcium*;
Carbon Monoxide;
Colitis;
Colon*;
Down-Regulation;
Epithelial Cells*;
Epithelium;
Flunarizine;
Heme;
HT29 Cells;
Humans*;
Iron;
Metabolism;
NF-kappa B*;
Tumor Necrosis Factor-alpha;
Verapamil
- From:Korean Journal of Anatomy
2006;39(5):401-406
- CountryRepublic of Korea
- Language:English
-
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.
