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Lithium Chloride Induces TNFα in Mouse Macrophages Via MEK–ERK‐Dependent Pathway
Author(s) -
Hull Megan,
Lee Eunhee,
Lee Taehyung,
Anand Nandita,
LaLone Ver,
Parameswaran Narayanan
Publication year - 2014
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24634
Subject(s) - tlr2 , trif , tumor necrosis factor alpha , mapk/erk pathway , inflammation , tlr3 , microbiology and biotechnology , signal transduction , stimulation , receptor , chemistry , innate immune system , immune system , tlr4 , lithium (medication) , toll like receptor , biology , immunology , biochemistry , endocrinology
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. J. Cell. Biochem. 115: 71–80, 2014. © 2013 Wiley Periodicals, Inc.