Abstract:
:Lithium is an anti-depressant drug that also possesses immunomodulatory functions. The anti-inflammatory effect of lithium is thought to involve activation of the transcription factor CREB, although the underlying mechanism is incompletely understood. We show here that in macrophages lithium stimulates Tpl2, a MAP kinase kinase kinase (MAP3K) known to mediate activation of extracellular signal regulated kinase (ERK) and the downstream target CREB. Lithium activates Tpl2 by inducing degradation of p105, an NF-kappaB precursor protein that functions as a physiological inhibitor of Tpl2. This novel function of lithium does not involve inhibition of a well-characterized lithium target, GSK3beta, since other known GSK3beta inhibitors do not induce p105 degradation or Tpl2 activation. Lithium also promotes the activation of Tpl2 and ERK by the TLR4 ligand LPS. On the other hand, prolonged incubation of macrophages with lithium results in dramatic loss of p105 and inhibition of LPS-stimulated NF-kappaB activation. Consequently, lithium both attenuates LPS-mediated pro-inflammatory gene induction and induces apoptosis in macrophages. These results provide novel insight into the anti-inflammatory function of lithium.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Zhang M,Jin W,Zhou X,Yu J,Lee AJ,Sun SCdoi
10.1016/j.cellsig.2008.12.010subject
Has Abstractpub_date
2009-04-01 00:00:00pages
559-66issue
4eissn
0898-6568issn
1873-3913pii
S0898-6568(08)00393-8journal_volume
21pub_type
杂志文章abstract::The numerous examples of "crosstalk" between signal transduction pathways reported in the biochemical literature seem to imply a general common response of cells to different stimuli, even when these stimuli act initially on different cascades. This contradicts our knowledge of the specificity of action of extracellul...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
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journal_title:Cellular signalling
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journal_title:Cellular signalling
pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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journal_title:Cellular signalling
pub_type: 杂志文章
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2013.03.025
更新日期:2013-08-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2017.04.009
更新日期:2017-07-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.09.004
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(03)00088-3
更新日期:2003-12-01 00:00:00
abstract:BACKGROUND:Our previous study showed that human omental adipose-derived stem cells (ADSCs) promote ovarian cancer growth and metastasis. In this study, the role of autophagy in the ovarian cancer-promoting effects of omental ADSCs was further determined. METHODS:The growth and invasion of ovarian cancer cells were det...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2020.109549
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.01.022
更新日期:2009-05-01 00:00:00
abstract::Differential regulation of PLC-beta 1 and -beta 2 by the G-protein alpha-subunit, G alpha 11, and by G-protein beta gamma-subunits was studied utilizing recombinant PLC-beta 1 and -beta 2. Rat PLC-beta 1 and human PLC-beta 2 were purified after recombinant baculovirus-mediated expression in Sf9 cells. The catalytic pr...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(95)00039-r
更新日期:1995-09-01 00:00:00
abstract::Glycogen synthase kinase 3beta (GSK3beta) is implicated in many biological events, including embryonic development, cell differentiation, apoptosis, and the insulin response. GSK3beta also plays a key role in the Wnt/beta-catenin pathway. The master regulator of the pigmentation microphthalmia-associated transcription...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.06.001
更新日期:2008-10-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.05.016
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journal_title:Cellular signalling
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更新日期:2011-02-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
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更新日期:2002-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2015-09-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
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更新日期:1995-03-01 00:00:00
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journal_title:Cellular signalling
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.04.006
更新日期:2008-08-01 00:00:00
abstract::In this work, we used colon carcinoma cell-line HCT116 to study the involvement of the 86-kDa subunit (Ku86) of DNA-protein kinase (DNA-PK) in human tumoural cell proliferation. We transfected these cells with a 639-bp cDNA encoding a Ku86 portion inserted into pcDNA3.1 vector in the antisense orientation. After selec...
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pub_type: 杂志文章
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