Fluoride in low concentration modifies expression and activity of 15 lipoxygenase in human PBMC differentiated monocyte/macrophage

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• 作者：I. Gutowska^a ; ^{gutowska@pum.edu.pl} ; I. Baranowska-Bosiacka^b ; K. Safranow^b ; K. Jakubowska^b ; ^c ; M. Olszewska^d ; A. Telesiń ; ski^e ; A. Siennicka^f ; M. Droź ; dzik^g ; D. Chlubek^b ; E. Stachowska^a
• 关键词：Fluoride ; 15 lipoxygenase-1 ; 15 lipoxygenase-2 ; Inflammation ; Macrophage
• 刊名：Toxicology
• 出版年：2012
• 期刊代码：47_0300483x
• 类别：pha
• 出版时间：16 May, 2012
• 卷：295
• 期：1-3
• 页码：23-30
• 文件大小：665 K

摘要

Epidemiological and experimental evidences demonstrate positive correlation between environmental and occupational fluoride exposure and risk to various cardio-respiratory disorders. That fore we decided to examine the effect of fluorides on activity and expression of 15LOX enzyme which is implicated in biosynthesis of inflammatory mediators. Expression of 15LOX-1 and -2 enzymes mRNA and protein was analyzed using RT PCT and immunoblotting methods respectively whereas HPLC method was used to measure the levels of 15 lipoxygenases end products. Additionally AA and LA concentration in cells was measured using GC method. We observed that fluoride in small concentration may significantly decrease activity of 15LOX-1 and -2 in human PBMC macrophages and then concentration of its end products: 15-HETE, 12-HETE and 9+13-HODE, what may cause development of inflammation through the cholesterol arrest into the macrophages and its differentiation to foam cell. Noted by our team overexpression of the 15LOX-1 enzyme in macrophages after addition of lowest fluoride concentrations (1 and 3 渭M) may be aimed at fighting inflammation development and excessive intracellular lipid accumulation. But highest fluoride concentrations (6 and 10 渭M) added to cell culture slowly declined expression of this enzyme probably because of developing inflammation. Additional 15LOX-2 expression in macrophages after fluoride addition was low in 1 and 3 渭M concentrations, but increased significantly after 10 渭M fluoride addition what may suggest developing acute inflammation, because 15LOX-2 is associated to increased local hypoxia. This study indicated that even in small concentrations fluorides changes the amounts and activity of 15 LOX-1 and -2 enzymes taking part in the development of inflammatory process.