title: Lithium chloride induces TNFα in mouse macrophages via MEK-ERK-dependent pathway.
abstract: Lithium (Li) is one of the currently prescribed drugs for bipolar disorders (BPDs) and has many neuro-regulatory and immune-modulating properties. Because many neuro-pathological diseases including BPDs have been associated with some level of inflammation, Li's effect on inflammation may have some crucial consequences. Even though Li has been shown to have pro- and anti-inflammatory activities in different cell models, mechanisms involved in these effects are not well understood. Moreover, Li's effect on inflammation in the presence of activators of Toll-like receptors (TLRs), especially TLR-2 (that activates MyD88-dependent pathway) and TLR-3 (that activates TRIF-dependent pathway) is not known. Here we tested the role of Li in the presence and absence of TLR2, and TLR3 on MAPK and NFκB pathways and the consequent production of tumor necrosis factor-α (TNFα) in Raw264.7 macrophages. Our results indicate that Li enhances TNFα production both in the absence and presence of TLR stimulation. Interestingly, Li differentially modulates MAPK and NFκB pathways in the absence and presence of TLR2/3 ligands. Our results further indicate that the effect of Li on TNFα occurs at the post-transcriptional level. Together, these studies demonstrate that Li induces TNFα production in macrophages and that it modulates signaling at different levels depending on the presence or absence of TLR2/3 stimulation.
authors.affiliation: Department of Physiology and Division of Pathology, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Hull
authors.affiliation: Department of Physiology and Division of Pathology, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Eunhee
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Physiology and Division of Pathology, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Taehyung
authors.initials: T
authors.lastname: Lee
authors.affiliation: Department of Physiology and Division of Pathology, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Nandita
authors.initials: N
authors.lastname: Anand
authors.affiliation: Department of Physiology and Division of Pathology, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Vernon
authors.initials: V
authors.lastname: LaLone
authors.affiliation: Department of Physiology and Division of Pathology, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Parameswaran
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002460:Cell Line / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000873:Anthracenes; D016328:NF-kappa B; C495342:TLR2 protein, human; C519703:TLR3 protein, mouse; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D014409:Tumor Necrosis Factor-alpha; C432165:pyrazolanthrone; D048670:MAP Kinase Kinase 4; D018021:Lithium Chloride
keywords: MACROPHAGE; TLR2; TLR3; TNFα
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