Cyclooxygenase-1 as the main source of proinflammatory factors after sodium orthovanadate treatment.
Vanadium is a metal present in air pollution. Its compounds may have both anticancer and carcinogenic properties. Vanadium compounds are tested in treatment of diabetes and cancer. An important research direction aimed at better understanding of the mechanisms of action of the vanadium compounds is a more detailed insight into their impact on inflammatory reactions. The aim of this study was to examine the effect of micromolar concentrations of sodium orthovanadate, Na3VO4, on the activity and expression of cyclooxygenases: COX-1 and COX-2. PMA-activated THP-1 macrophages were incubated in vitro for 48 h with micromolar concentrations of sodium orthovanadate. As shown by an ELISA assay, sodium orthovanadate increases the quantity of prostaglandin E2 being released into the medium in a dose-dependent manner as well as impacts the quantity of the stable metabolite of thromboxane A2: thromboxane B2. The use of a COX-2 inhibitor, NS-398, revealed that this effect was independent of changes in the activity of COX-2. Western blotting analysis showed that sodium orthovanadate increased the expression of COX-2 when used with NS-398. Quantitative real-time PCR measurements of mRNA levels of genes PTGS1 and PTGS2 revealed no effect of the tested vanadium compound on the levels of analyzed transcripts.
Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72 Av., 70-111, Szczecin, Poland, jan.korbecki@onet.eu.
Jan
J
Korbecki
Irena
I
Baranowska-Bosiacka
Izabela
I
Gutowska
Katarzyna
K
Piotrowska
Dariusz
D
Chlubek
D000393:Air Pollutants / Q000633:toxicity*; D045744:Cell Line, Tumor; D051545:Cyclooxygenase 1 / Q000096:biosynthesis*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis; D014638:Vanadates / Q000633:toxicity*
D000393:Air Pollutants; D018836:Inflammation Mediators; D012333:RNA, Messenger; D014638:Vanadates; D013929:Thromboxane B2; D013928:Thromboxane A2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D015232:Dinoprostone