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 CdCl2 or HgCl2. MeHg was known to induce cytosolic phospholipase A2 (PLA2) 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 PLA2 activation was necessary for MeHg induced IL-6 release. Results indicated that AACOCF3 (≥10 μM), MAFP (≥0.625 μM) and BEL (≥0.625 μM) significantly reduced MeHg induced IL-6 release in glia. However, these PLA2 inhibitors did not block MeHg induced GSH depletion. These results suggested that PLA2 activation was required for MeHg to induce glial IL-6 release.