The Lack of Association between FCN2 Gene Promoter Region Polymorphisms and Dental Caries in Polish Children.

The aim of this study was to examine the association of single-nucleotide polymorphisms (SNPs) in the gene encoding ficolin-2 protein (FCN2 gene) at positions -986 (rs17514136), -602 (rs3124953), and -4 (rs3124952) with dental caries in Polish children. Two hundred and sixty Polish Caucasian children aged 15 years were enrolled in this study: 82 with "higher" caries experience (DMFT >5) and 178 with "lower" caries experience (DMFT ≤5). In addition, subjects with caries experience (DMFT ≥1) and caries-free subjects (DMFT = 0) were compared. FCN2 SNPs were genotyped with PCR-RFLP methods. There were no significant differences in the genotype, allele, or haplotype distributions in 3 analyzed SNPs of the FCN2 gene between children with "higher" and those with "lower" caries experience as well as between children with caries experience and caries-free children. In conclusion, we did not find any association of FCN2 promoter polymorphisms at positions -986, -602, and -4 with dental caries in Polish children.

Beer as a Rich Source of Fluoride Delivered into the Body.

Fluoride is an element which in the minimum amount is necessary for the proper construction of the teeth and bones. But on the other hand, it increases the synthesis of reactive oxygen species, inflammatory mediators, and impairs the action of enzymes. Beer is the most popular alcoholic beverage in the world. Due to its prevalence and volume of consumption, it should be considered as a potential source of F- and taken into account in designing a balanced diet. Therefore, the aim of this study was to analyze beer samples in terms of F- levels. The concentrations of fluoride were examined using ion-selective electrode Thermo Scientific Orion and statistical analysis was based on two-way ANOVA and t test. When compared to imported beers, Polish beers were characterized by the lowest mean F- concentration (0.089 ppm). The highest mean F- concentrations were recorded in beers from Thailand (0.260 ppm), Italy (0.238 ppm), Mexico (0.210 ppm), and China (0.203 ppm). Our study shows that beer is a significant source of fluoride for humans, which is mainly associated with the quality of the water used in beer production.

Fluoride as a factor initiating and potentiating inflammation in THP1 differentiated monocytes/macrophages.

It is well known that exposure to fluorides lead to an increased ROS production and enhances the inflammatory reactions. Therefore we decided to examine whether cyclooxygenases (particular COX-2) activity and expression may be changed by fluoride in THP1 macrophages and in this way may change the prostanoids biosynthesis. In the present work we demonstrate that fluoride increased concentration of PGE2 and TXA2 in THP1 macrophages. Following exposure to 1-10 µM NaF, COX-2 protein and COX-2 transcript increased markedly. COX-2 protein up-regulation probably is mediated by ROS, produced during fluoride-induced inflammatory reactions. Additional fluoride activates the transcription factor, nuclear factor (NF)-kappaB, which is involved in the up-regulation of COX-2 gene expression. This study indicated that even in small concentrations fluoride changes the amounts and activity of COX-1 and COX-2 enzymes taking part in the initiating and development of inflammatory process.

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

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 µM) may be aimed at fighting inflammation development and excessive intracellular lipid accumulation. But highest fluoride concentrations (6 and 10 µM) 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 µM concentrations, but increased significantly after 10 µM 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.

Activation of phospholipase A(2) by low levels of fluoride in THP1 macrophages via altered Ca(2+) and cAMP concentration.

Phospholipases (PLA's) participate in the regulation of physiological and pathological processes in the cell, including the release of pro-inflammatory mediators and stimulation of inflammatory processes. It is also well known that fluoride can increase the inflammatory reactions. Therefore we decided to examine the effect of fluorides in concentrations determined in human serum on cPLA(2) and sPLA(2) activity. The incubation of macrophages in fluoride solutions significantly increased the amount of synthesized cellular cAMP, intracellular calcium and sPLA(2) activity in a dose-dependent pattern. The cPLA(2) activity, estimated by the amount of released arachidonic acid, increased significantly when 10 µM NaF was used. The results of our study suggest that fluoride may change the activity of phospholipases in macrophage cells. Probably, increased cAMP concentration activates protein kinase C (PKC) and thus stimulates PLA(2). cAMP also regulates the passage of Ca(2+) through ion channels, which additionally influence PLA(2) throughout Ca(2+)-calmodulin dependent protein kinase.