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Cobalt Chloride Attenuates Oxidative Stress and Inflammation through NF-κB Inhibition in Human Renal Proximal Tubular Epithelial Cells
- Source :
- Journal of Korean Medical Science
- Publication Year :
- 2014
- Publisher :
- The Korean Academy of Medical Sciences, 2014.
-
Abstract
- We evaluated the effect of cobalt chloride (CoCl2) on TNF-α and IFN-γ-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-α/IFN-γ. 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-α/IFN-γ. TNF-α/IFN-γ-treated-cells showed an increase in the nuclear translocation of phosphorylated NF-κBp65 protein, the DNA-binding activity of NF-κBp50 and NF-κB transcriptional activity and a decrease in IκBα 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-α/IFN-γ-treated cells. We demonstrated that this effect was mediated through NF-κB signaling because an NF-κB 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-α/IFN-γ-induced inflammation through the inhibition of NF-κB and ROS in HK-2 cells. However, CoCl2 appears to act in an HO-1-independent manner. Graphical Abstract
- Subjects :
- T cell
Renal Tubular Epithelial Cells
Inflammation
Biology
medicine.disease_cause
Cell Line
Kidney Tubules, Proximal
Interferon-gamma
medicine
Nuclear Factor-kappa B
Humans
Phosphorylation
RNA, Small Interfering
Hemeoxygenase-1
Chemokine CCL5
Chemokine CCL2
Gene knockdown
Tumor Necrosis Factor-alpha
Monocyte
Cobalt Chloride
NF-kappa B
Transcription Factor RelA
NF-kappa B p50 Subunit
Epithelial Cells
General Medicine
Cobalt
Molecular biology
IκBα
Oxidative Stress
medicine.anatomical_structure
Cell culture
Tumor necrosis factor alpha
Original Article
RNA Interference
medicine.symptom
Oxidative stress
Heme Oxygenase-1
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 15986357 and 10118934
- Volume :
- 29
- Issue :
- Suppl 2
- Database :
- OpenAIRE
- Journal :
- Journal of Korean Medical Science
- Accession number :
- edsair.doi.dedup.....dbd8e9bbe79efe075d99e4011d3ef125