Applied Cell Biology

Pharmacological inhibition of NF-kB activity prevents methylmercury induced glial IL-6 release

Jason Y.Chang, Tarun K.Garg Pharmacological inhibition of NF-kB activity prevents methylmercury induced glial IL-6 release.

Department ofNeurobiology&Developmental Sciences, College ofMedicine,University of Arkansas forMedical Sciences, Little Rock,AR 72205, (USA)
#Myeloma Institute forResearch andTherapy,Winthrop P. RockefellerCancer Institute,University of Arkansas forMedical Sciences, Little Rock,AR 72205, (USA)

Abstract

Methylmercury (MeHg) is an environmental toxin that can alter a number of cellular events in cells derived fromthe nervous system.We previously demonstrated that MeHg could cause interleukin-6 (IL-6) release in various glial cell types. Activation of phospholipase C and phospholipase A₂ were required for this event. Using primary mouse glial cultures as an experimental model, this studywas designed to further determine intracellular signaling pathways involved in this IL-6 induction. Specifically, we
tested the hypothesis that NF-kB activation was critically important for MeHg induced IL-6 production. Results using various NF-kB inhibitors (BAY-117082, TPCA-1, 15d-PGJ2 and curcumin) indicated thatNF-kB activationwas required forMeHg induced IL-6 production. Furthermore, BAY-117082, 15d-PGJ2 and curcumin showed various degrees of protective effects against a cytotoxic concentration of MeHg.

Keywords:

IL-6; Methylmercury; NF-kB.