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

• Published in: Prostaglandins, leukotrienes and essential fatty acids leukotrienes and essential fatty acids, 2012-03, Vol.86 (3), p.99-105
• Main Authors: Gutowska, I, Baranowska-Bosiacka, I, Siennicka, A, Telesiński, A, Stańczyk-Dunaj, M, Wesołowska, T, Gąssowska, M, Kłos, P, Zakrzewska, H, Machaliński, B, Chlubek, D, Stachowska, E
• Format: Article
• Language: English
• Subjects: Calcium - metabolism; Cells, Cultured; Cyclic AMP - metabolism; Enzyme Activation; Humans; Macrophages - metabolism; Phospholipases A2 - metabolism; Sodium Fluoride - pharmacology
• ISSN: 1532-2823
• DOI: 10.1016/j.plefa.2012.02.002

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.