title: Cobalt chloride attenuates oxidative stress and inflammation through NF-κB inhibition in human renal proximal tubular epithelial cells.
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.
authors.affiliation: Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea.
authors.forename: Se Won
authors.identifier: 0000-0003-3795-9322
authors.initials: SW
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Yun-Mi
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sejoong
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ho Jun
authors.identifier: 0000-0003-1185-2631
authors.initials: HJ
authors.lastname: Chin
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Chae
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ki Young
authors.identifier: 0000-0002-8872-8236
authors.initials: KY
authors.lastname: Na
mesh_terms: D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D003035:Cobalt / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C111835:CCL2 protein, human; C483024:CCL5 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D003035:Cobalt; D007371:Interferon-gamma; D051547:Heme Oxygenase-1; C018021:cobaltous chloride
keywords: Cobalt Chloride; Hemeoxygenase-1; Inflammation; Nuclear Factor-kappa B; Renal Tubular Epithelial Cells