title: The Effect of Cadmium on COX-1 and COX-2 Gene, Protein Expression, and Enzymatic Activity in THP-1 Macrophages.
abstract: The aim of this study was to examine the effects of cadmium in concentrations relevant to those detected in human serum on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) expression at mRNA, protein, and enzyme activity levels in THP-1 macrophages. Macrophages were incubated with various cadmium chloride (CdCl2) solutions for 48 h at final concentrations of 5 nM, 20 nM, 200 nM, and 2 μM CdCl2. The mRNA expression and protein levels of COXs were analyzed with RT-PCR and Western blotting, respectively. Prostaglandin E2 (PGE2) and stable metabolite of thromboxane B2 (TXB2) concentrations in culture media were determined using ELISA method. Our study demonstrates that cadmium at the highest tested concentrations modulates COX-1 and COX-2 at mRNA level in THP-1 macrophages; however, the lower tested cadmium concentrations appear to inhibit COX-1 protein expression. PGE2 and TXB2 production is not altered by all tested Cd concentrations; however, the significant stimulation of PGE2 and TXB2 production is observed when macrophages are exposed to both cadmium and COX-2 selective inhibitor, NS-398. The stimulatory effect of cadmium on COXs at mRNA level is not reflected at protein and enzymatic activity levels, suggesting the existence of some posttranscriptional, translational, and posttranslational events that result in silencing of those genes' expression.
authors: Department of Hygiene and Epidemiology, Pomeranian Medical University, Powstańców Wlkp. 72 Av, 70-111, Szczecin, Poland.
authors: Tomasz
authors: T
authors: Olszowski
authors: Izabela
authors: I
authors: Gutowska
authors: Irena
authors: I
authors: Baranowska-Bosiacka
authors: Katarzyna
authors: K
authors: Piotrowska
authors: Jan
authors: J
authors: Korbecki
authors: Mateusz
authors: M
authors: Kurzawski
authors: Dariusz
authors: D
authors: Chlubek
mesh_terms: D019256:Cadmium Chloride / Q000737:chemistry*; D002460:Cell Line; D003470:Culture Media; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D020868:Gene Silencing; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D009578:Nitrobenzenes / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D013449:Sulfonamides / Q000737:chemistry; D013928:Thromboxane A2 / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
chemical_list: D003470:Culture Media; D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D013929:Thromboxane B2; D013928:Thromboxane A2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D019256:Cadmium Chloride; D015232:Dinoprostone
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