title: Methylmercury-induced IL-6 release requires phospholipase C activities.
abstract: Methylmercury (MeHg) is a neurotoxin capable of causing severe damage to the CNS, especially in the developing fetus. Glia in the CNS release a number of cytokines that are important for proper CNS development and function. We reported earlier that MeHg could induce interleukin-6 (IL-6) release in primary mouse glia. This finding is significant considering previous reports indicating that sustained IL-6 exposure could be detrimental to cerebellar granule neurons, one of the major cellular targets of MeHg cytotoxicity. By using pharmacological antagonists against phophatidycholine- and phosphoinositol-specific phospholipase C, the current study indicated that phospholipase C activity was necessary for MeHg-induced IL-6 release. Results from pharmacological antagonists further suggested that the calcium signaling initiated by phospholipase C appeared essential for this event. In contrast, protein kinase C activity did not appear to be important. Even though mitogen-activated protein kinases were important for IL-6 release in some experimental systems, these enzymes did not appear to be required for MeHg-induced IL-6 release in glia. Based on these data and those reported by us and others, there is a possibility that MeHg-induced phospholipase C activation initiates a calcium signaling that causes phospholipase A(2) activation. This, in turn, leads to arachidonic acid and lysophosphatidyl choline generation, both of which are potent inducers for IL-6 release.
authors.affiliation: Department of Neurobiology and Developmental Sciences, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. changjasony@uams.edu
authors.forename: Jason Y
authors.initials: JY
authors.lastname: Chang
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D015850:Interleukin-6 / Q000378:metabolism*; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009457:Neuroglia / Q000378:metabolism; D054467:Phospholipases A2 / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D015850:Interleukin-6; D008767:Methylmercury Compounds; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D054467:Phospholipases A2; D010738:Type C Phospholipases