Activation of phospholipase A2 by low levels of fluoride in THP1 macrophages via altered Ca2+ 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 cPLA2 and sPLA2 activity. The incubation of macrophages in fluoride solutions significantly increased the amount of synthesized cellular cAMP, intracellular calcium and sPLA2 activity in a dose-dependent pattern. The cPLA2 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 PLA2. cAMP also regulates the passage of Ca2+ through ion channels, which additionally influence PLA2 throughout Ca2+-calmodulin dependent protein kinase.