IL-6 release from mouse glia caused by MeHg requires cytosolic phospholipase A2 activation.
Methylmercury is a potent neurotoxin that causes severe neurological disorders in fetuses and young children. Recent studies indicated that MeHg could alter levels of immune mediators produced by cells of the central nervous system. Results from this study indicated that MeHg could greatly induce IL-6 release from primary mouse glial cultures. This property was not shared by other cytotoxic heavy metals, such as CdCl(2) or HgCl(2). MeHg was known to induce cytosolic phospholipase A(2) (PLA(2)) activation and expression, and this enzyme was required for IL-6 induction in some experimental systems. Further experiments using structurally distinct pharmacological agents were performed to test the hypothesis that MeHg induced PLA(2) activation was necessary for MeHg induced IL-6 release. Results indicated that AACOCF(3) (>or=10 microM), MAFP (>or=0.625 microM) and BEL (>or=0.625 microM) significantly reduced MeHg induced IL-6 release in glia. However, these PLA(2) inhibitors did not block MeHg induced GSH depletion. These results suggested that PLA(2) activation was required for MeHg to induce glial IL-6 release.
Chang
Jason Y
JY
Department of Neurobiology and Developmental Sciences, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. changjasony@uams.edu
Tsai
Pao-Feng
PF
D000818:Animals; D000831:Animals, Newborn; D019256:Cadmium Chloride / Q000633:toxicity; D002540:Cerebral Cortex / Q000166:cytology; D003600:Cytosol / Q000187:drug effects* / Q000201:enzymology; D004789:Enzyme Activation; D015850:Interleukin-6 / Q000096:biosynthesis*; D008627:Mercuric Chloride / Q000633:toxicity; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism*
D015850:Interleukin-6; D008767:Methylmercury Compounds; D064801:Phospholipase A2 Inhibitors; D008627:Mercuric Chloride; D054467:Phospholipases A2; D019256:Cadmium Chloride