Cobalt Chloride Attenuates Oxidative Stress and Inflammation through NF-kappaB Inhibition in Human Renal Proximal Tubular Epithelial Cells.
10.3346/jkms.2014.29.S2.S139
- Author:
Se Won OH
1
;
Yun Mi LEE
;
Sejoong KIM
;
Ho Jun CHIN
;
Dong Wan CHAE
;
Ki Young NA
Author Information
1. Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Cobalt Chloride;
Hemeoxygenase-1;
Inflammation;
Nuclear Factor-kappa B;
Renal Tubular Epithelial Cells
- MeSH:
Cell Line;
Chemokine CCL2/metabolism;
Chemokine CCL5/metabolism;
Cobalt/*pharmacology;
Epithelial Cells/cytology/metabolism;
Heme Oxygenase-1/antagonists & inhibitors/genetics/metabolism;
Humans;
*Inflammation;
Interferon-gamma/pharmacology;
Kidney Tubules, Proximal/cytology;
NF-kappa B/antagonists & inhibitors/genetics/*metabolism;
NF-kappa B p50 Subunit/genetics/metabolism;
Oxidative Stress/*drug effects;
Phosphorylation;
Protein Binding;
RNA Interference;
RNA, Small Interfering/metabolism;
Transcription Factor RelA/metabolism;
Tumor Necrosis Factor-alpha/pharmacology
- From:Journal of Korean Medical Science
2014;29(Suppl 2):S139-S145
- CountryRepublic of Korea
- Language:English
-
Abstract:
We evaluated the effect of cobalt chloride (CoCl2) on TNF-alpha and IFN-gamma-induced-inflammation and reactive oxygen species (ROS) in renal tubular epithelial cells (HK-2 cells). We treated HK-2 cells with CoCl2 before the administration of TNF-alpha/IFN-gamma. To regulate hemeoxygenase-1 (HO-1) expression, the cells were treated CoCl2 or HO-1 siRNA. CoCl2 reduced the generation of ROS induced by TNF-alpha/IFN-gamma. TNF-alpha/IFN-gamma-treated-cells showed an increase in the nuclear translocation of phosphorylated NF-kappaBp65 protein, the DNA-binding activity of NF-kappaBp50 and NF-kappaB transcriptional activity and a decrease in IkappaBalpha protein expression. These changes were restored by CoCl2. We noted an intense increase in monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normal T cell expressed and secreted (RANTES) production in TNF-alpha/IFN-gamma-treated cells. We demonstrated that this effect was mediated through NF-kappaB signaling because an NF-kappaB inhibitor significantly reduced MCP-1 and RANTES production. CoCl2 effectively reduced MCP-1 and RANTES production. The expression of HO-1 was increased by CoCl2 and decreased by HO-1 siRNA. However, knockdown of HO-1 by RNA interference did not affect MCP-1 or RANTES production. We suggest that CoCl2 has a protective effect on TNF-alpha/IFN-gamma-induced inflammation through the inhibition of NF-kappaB and ROS in HK-2 cells. However, CoCl2 appears to act in an HO-1-independent manner.
