PMID- 25317018 OWN - NLM STAT- MEDLINE DCOM- 20150616 LR - 20211021 IS - 1598-6357 (Electronic) IS - 1011-8934 (Print) IS - 1011-8934 (Linking) VI - 29 Suppl 2 IP - Suppl 2 DP - 2014 Sep TI - Cobalt chloride attenuates oxidative stress and inflammation through NF-kappaB inhibition in human renal proximal tubular epithelial cells. PG - S139-45 LID - 10.3346/jkms.2014.29.S2.S139 [doi] AB - 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. FAU - Oh, Se Won AU - Oh SW AUID- ORCID: 0000-0003-3795-9322 AD - Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea. FAU - Lee, Yun-Mi AU - Lee YM AD - Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. FAU - Kim, Sejoong AU - Kim S AD - Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. FAU - Chin, Ho Jun AU - Chin HJ AUID- ORCID: 0000-0003-1185-2631 AD - Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. FAU - Chae, Dong-Wan AU - Chae DW AD - Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. FAU - Na, Ki Young AU - Na KY AUID- ORCID: 0000-0002-8872-8236 AD - Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. LA - eng PT - Journal Article DEP - 20140930 PL - Korea (South) TA - J Korean Med Sci JT - Journal of Korean medical science JID - 8703518 RN - 0 (CCL2 protein, human) RN - 0 (CCL5 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL5) RN - 0 (NF-kappa B) RN - 0 (NF-kappa B p50 Subunit) RN - 0 (RNA, Small Interfering) RN - 0 (Transcription Factor RelA) RN - 0 (Tumor Necrosis Factor-alpha) RN - 3G0H8C9362 (Cobalt) RN - 82115-62-6 (Interferon-gamma) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EVS87XF13W (cobaltous chloride) SB - IM MH - Cell Line MH - Chemokine CCL2/metabolism MH - Chemokine CCL5/metabolism MH - Cobalt/*pharmacology MH - Epithelial Cells/cytology/metabolism MH - Heme Oxygenase-1/antagonists & inhibitors/genetics/metabolism MH - Humans MH - *Inflammation MH - Interferon-gamma/pharmacology MH - Kidney Tubules, Proximal/cytology MH - NF-kappa B/antagonists & inhibitors/genetics/*metabolism MH - NF-kappa B p50 Subunit/genetics/metabolism MH - Oxidative Stress/*drug effects MH - Phosphorylation MH - Protein Binding MH - RNA Interference MH - RNA, Small Interfering/metabolism MH - Transcription Factor RelA/metabolism MH - Tumor Necrosis Factor-alpha/pharmacology PMC - PMC4194284 OTO - NOTNLM OT - Cobalt Chloride OT - Hemeoxygenase-1 OT - Inflammation OT - Nuclear Factor-kappa B OT - Renal Tubular Epithelial Cells COIS- The authors have no potential conflicts of interest relevant to this article to disclose. EDAT- 2014/10/16 06:00 MHDA- 2015/06/17 06:00 PMCR- 2014/09/01 CRDT- 2014/10/16 06:00 PHST- 2014/05/10 00:00 [received] PHST- 2014/07/03 00:00 [accepted] PHST- 2014/10/16 06:00 [entrez] PHST- 2014/10/16 06:00 [pubmed] PHST- 2015/06/17 06:00 [medline] PHST- 2014/09/01 00:00 [pmc-release] AID - 10.3346/jkms.2014.29.S2.S139 [doi] PST - ppublish SO - J Korean Med Sci. 2014 Sep;29 Suppl 2(Suppl 2):S139-45. doi: 10.3346/jkms.2014.29.S2.S139. Epub 2014 Sep 30.