共查询到20条相似文献,搜索用时 593 毫秒
1.
2.
Nakaizumi A Horie T Kida T Kurimoto T Sugiyama T Ikeda T Oku H 《Cellular and molecular neurobiology》2012,32(1):95-106
Modulation of enzyme activity through nitrosylation has recently been identified as a new physiological activity of nitric
oxide (NO). We hypothesized that NO enhances the TNF-α-induced death of retinal neurons through a suppression of nuclear factor-κB
(NF-κB) by nitrosylation. In this study, cells from the RGC-5 line were exposed to different concentrations (2.0, 10, and
50 ng/ml) of TNF-α, and the degree of TNF-α-induced cell death was determined by the WST-8 assay and by flow cytometric measurements
of the externalization of phosphatidylserine. The effects of etanercept, a soluble TNFR-Fc fusion protein, and S-nitroso-N-penicillamine (SNAP), an NO donor, on the toxicity were determined. Experiments were also performed to determine whether
nitric oxide synthase (NOS) was associated with the toxicity of TNF-α. The activation of NF-κB was determined by the detection
of the p65 subunit in the nuclear extracts. Our results showed that exposure of RGC-5 cells to different concentrations of
TNF-α significantly decreased the number of living cells in a dose-dependent way. The death was partially due to apoptosis
with an externalization of phosphatidylserine, and the death was suppressed by etanercept. Exposure to TNF-α increased the
activation of NF-κB and the expression of iNOS. Although NF-κB inhibitors suppressed the increase of iNOS, they also potentiated
the TNF-α-induced death. Both L-NAME and aminoguanidine, both NOS inhibitors, rescued the cells from death. In contrast, addition
of SNAP caused nitrosylation of the inhibitory κB kinase, and suppressed the NF-κB activation and potentiated the TNF-α-induced
neurotoxicity. These results indicate that NO potentiates the neurotoxicity of TNF-α by suppressing NF-κB. 相似文献
3.
H2 is a therapeutic antioxidant that can reduce oxidative stress. Oxidized low-density lipoprotein, which plays roles in atherosclerosis,
may promote endothelial dysfunction by binding the cell-surface receptor LOX-1. LOX-1 expression can be upregulated by various
stimuli, including TNF-α. Thus, we aimed to examine whether the upregulation of LOX-1 by different stimuli could be blocked
by H2 in endothelial cells. H2 significantly abolished the upregulation of LOX-1 by different stimuli, including TNF-α, at the protein and mRNA levels.
The TNF-α-induced upregulation of LOX-1 was also attenuated by the NF-κB inhibitor N-acetyl-l-cysteine. H2 inhibited the TNF-α-induced activation of NF-κB and the phosphorylation of IκB-α. Furthermore, H2 inhibited the expression of LOX-1 and the activation of NF-κB in apolipoprotein E knockout mice, an animal model of atherosclerosis.
Thus, H2 probably inhibits cytokine-induced LOX-1 gene expression by suppressing NF-κB activation. 相似文献
4.
Lee S Park HH Son HY Ha JH Lee MG Oh TY Sohn DH Jeong TC Lee SH Son JK Lee SG Jun CD Kim SH 《Cell biology and toxicology》2007,23(2):105-112
Mast cell-mediated allergic inflammation is involved in many diseases such as asthma, sinusitis, and rheumatoid arthritis.
Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin
(IL)-1β and IL-6 with immune regulatory properties. The formulated ethanol extract of Artemisia asiatica Nakai (DA-9601) has been reported to have antioxidative and anti-inflammatory activities. In this report, we investigated
the effect of DA-9601 on the expression of pro-inflammatory cytokines by the activated human mast cell line HMC-1 and studied
its possible mechanisms of action. DA-9601 dose-dependently decreased the gene expression and production of TNF-α, IL-1β,
and IL-6 on phorbol 12-myristate 13-acetate (PMA)- and calcium ionophore A23187-stimulated HMC-1 cells. In addition, DA-9601
attenuated PMA- and A23187-induced activation of NF-κB as indicated by inhibition of degradation of IκBα, nuclear translocation
of NF-κB, NF-κB/DNA binding, and NF-κB-dependent gene reporter assay. Our in vitro studies provide evidence that DA-9601 might contribute to the treatment of mast cell-derived allergic inflammatory diseases. 相似文献
5.
6.
7.
Changes in the levels of antiapoptotic protein B-cell lymphoma 2 (Bcl-2) protein has been reported in murine and human tuberculosis.
We investigated the role of mitogen-activated protein kinase pathways in the production of Bcl-2 protein in THP-1 human monocytes
infected with Mycobacterium tuberculosis H37Rv and H37Ra. Analysis of phosphorylation profiles of mitogen-activated protein kinase kinase-1, extracellular-signal
regulated kinase 1/2, mitogen-activated protein kinase kinase 3/6, and p38 mitogen-activated protein kinase; B-cell lymphoma
2 kinetics; and tumor necrosis factor-α (TNF-α) secretion levels showed variation between the two strains. Mycobacterium tuberculosis H37Rv induced higher Bcl-2 and lower TNF-α levels, whereas H37Ra the reverse. The strains also differed in their usage of
CD14 and human leukocyte antigen-DR receptors in mediating extracellular-signal regulated kinase 1/2 and p38 mitogen-activated
protein kinase activation. Mycobacterium tuberculosis H37Rv- and H37Ra-induced Bcl-2 production was reduced by specific inhibitors of mitogen-activated protein kinase kinase-1
(PD98059) and p38 (SB203580), but increased by nuclear factor κB (NF-κB) inhibitor (BAY 11-7082). TNF-α production by both
strains was reduced in the presence of specific inhibitors of mitogen-activated protein kinase kinase-1 (PD98059), p38 (SB203580),
and NF-κB (BAY 11-7082). Furthermore, inhibition of NF-κB was accompanied by an increase in strain-induced extracellular-signal
regulated kinase 1/2 phosphorylation. Collectively, these results indicate for the first time that the production of Bcl-2
and TNF-α by M. tuberculosis H37Rv/H37Ra-infected THP-1 human monocytes is mediated through mitogen-activated protein kinases and NF-κB. 相似文献
8.
Fei Guo Xiang Guo An Xie Yuan Lei Lou Yang Wang 《Biological trace element research》2011,142(3):693-703
Lanthanide ions have been proven to have various biologic effects. Lanthanum with extremely active physical and chemical property
was evidenced to possess antibacterial and immune adjustment effects. In the present study, the anti-inflammatory effects
of lanthanum chloride (LaCl3) on lipopolysaccharide (LPS)-challenged mice were examined in vivo and in vitro. The results indicated that LaCl3 can greatly decrease the secretion of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β as well as TNF-α mRNA expression
in the mice challenged with LPS. To clarify the mechanism involved, the effects of LaCl3 on the activation of nuclear factor (NF)-κB were examined both in liver and in peritoneal macrophages. The LPS-induced activation
of NF-κB was significantly blocked by LaCl3. These findings demonstrate that the inhibition of the LPS-induced inflammatory media, such as TNF-α and IL-1β, by LaCl3, is due to the inhibition of NF-κ B activation. 相似文献
9.
Sander W Tas Margriet J Vervoordeldonk Najat Hajji Michael J May Sankar Ghosh Paul P Tak 《Arthritis research & therapy》2006,8(4):R86-9
Nuclear factor (NF)-κB is a key regulator of synovial inflammation. We investigated the effect of local NF-κB inhibition in
rat adjuvant arthritis (AA), using the specific IκB kinase (IKK)-β blocking NF-κB essential modulator-binding domain (NBD)
peptide. The effects of the NBD peptide on human fibroblast-like synoviocytes (FLS) and macrophages, as well as rheumatoid
arthritis (RA) whole-tissue biopsies, were also evaluated. First, we investigated the effects of the NBD peptide on RA FLS
in vitro. Subsequently, NBD peptides were administered intra-articularly into the right ankle joint of rats at the onset of disease.
The severity of arthritis was monitored over time, rats were sacrificed on day 20, and tissue specimens were collected for
routine histology and x-rays of the ankle joints. Human macrophages or RA synovial tissues were cultured ex vivo in the presence or absence of NBD peptides, and cytokine production was measured in the supernatant by enzyme-linked immunosorbent
assay. The NBD peptide blocked interleukin (IL)-1-β-induced IκBα phosphorylation and IL-6 production in RA FLS. Intra-articular
injection of the NBD peptide led to significantly reduced severity of arthritis (p < 0.0001) and reduced radiological damage (p = 0.04). This was associated with decreased synovial cellularity and reduced expression of tumor necrosis factor (TNF)-α
and IL-1-β in the synovium. Incubation of human macrophages with NBD peptides resulted in 50% inhibition of IL-1-β-induced
TNF-α production in the supernatant (p < 0.01). In addition, the NBD peptide decreased TNF-α-induced IL-6 production by human RA synovial tissue biopsies by approximately
42% (p < 0.01). Specific NF-κB blockade using a small peptide inhibitor of IKK-β has anti-inflammatory effects in AA and human RA
synovial tissue as well as in two important cell types in the pathogenesis of RA: macrophages and FLS. These results indicate
that IKK-β-targeted NF-κB blockade using the NBD peptide could offer a new approach for the local treatment of arthritis. 相似文献
10.
The mechanism by which lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) induces production of proinflammatory
cytokines in murine macrophages, and the role of phosphatidylinositol 3-kinase (PI3-kinase) have not been well investigated.
Activation of nuclear factor κB (NF-κB) is initiated by the phosphorylation of the inhibitory subunit, IκB, which targets
IκB for degradation and leads to the release of active NF-κB. In this study we demonstrate that 2- (4-morpholinyl)-8-phenylchromone
(LY294002), which inhibits PI3-kinase, specifically inhibited degradation of IκBα in RAW264.7 cells stimulated with interferon-γ
(IFN-γ) plus LPS or IFN-γ plus PMA. To elucidate the importance of this activity in RAW264.7 cells, we examined tumor necrosis
factor-α (TNF-α) and interleukin IL)-6 production in the activated cells. Pretreatment of the cells with LY294002 resulted
in the inhibition of TNF-α and IL-6 production in RAW264.7 cells stimulated with IFN-γ plus LPS or IFN-γ plus PMA. Furthermore,
LY294002 inhibited the production of nitric oxide NO) in RAW264.7 cells stimulated with IFN-γ plus LPS or IFN-γ plus PMA.
LY294002 also inhibited inducible NO synthase (iNOS) mRNA expression in the activated RAW264.7 cells. In conclusion, the present
results suggest that PI3-kinase is involved in the signal transduction pathway responsible for LPS- or PMA-mediated TNF-α
and IL-6 production, and that LY294002 inhibits NO generation through blocking the degradation of IκBα in activated RAW264.7
cells.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
11.
12.
The present study attempts to investigate the effects of S-propargyl-cysteine (SPRC), a sulfur-containing amino acid, on lipopolysaccharide (LPS)-induced inflammatory response in H9c2
cardiac myocytes. We found that SPRC prevented nuclear factor-κB (NF-κB) activation assessed by NF-κB p65 phosphorylation
and IκBα degradation, suppressed LPS-induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and intracellular
reactive oxygen species (ROS) production. Furthermore, incubation of H9c2 cells with SPRC induced phosphorylation of Akt in
a time- and concentration-dependent manner. In addition, SPRC attenuated LPS-induced mRNA and protein expression of tumor
necrosis factor-α (TNF-α), and mRNA expression of intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase
(iNOS). The effects of SPRC were abolished by cystathionine γ-lyase [CSE-an enzyme that synthesizes hydrogen sulfide (H2S)] inhibitor, dl-propargylglycine (PAG), SPRC-induced Akt phosphorylation and TNF-α release was also abolished by the phosphoinositide 3-kinase
(PI3K) inhibitor LY294002. Furthermore, SPRC also increased LPS-induced down-regulation expression of CSE and H2S level in H9c2 cells. PAG abolished SPRC-induced up-regulation of H2S level. Therefore, we concluded that SPRC produced an anti-inflammatory effect in LPS-stimulated H9c2 cells partly through
the CSE/H2S pathway by impairing IκBα/NF-κB signaling and by activating PI3K/Akt signaling pathway. 相似文献
13.
14.
Michael Hoffmann Mathias Schmidt Winfried Wels 《Cancer immunology, immunotherapy : CII》1998,47(3):167-175
Tumor necrosis factor (TNF)-α has a broad range of biological activities, which depend heavily on cell type and physiological
condition. In a panel of human tumor cell lines we analyzed expression of the receptor tyrosine kinases EGFR, ErbB2 and ErbB3,
and the response to TNF-α. Among the cell lines tested those resistant to TNF-α were found to express high levels of either
EGFR, or ErbB2 and ErbB3. In TNF-sensitive breast and cervical carcinoma cells activation of EGFR or ErbB2 by the exogenous
growth factors EGF and heregulin β1 resulted in a significant increase in the number of cells surviving TNF-α treatment. In
contrast, inhibition of EGFR activation in TNF-resistant breast carcinoma cells by the novel antagonistic anti-EGFR antibody
14E1 sensitized the cells to the cytotoxic effects of TNF-α. A bacterially expressed fusion protein consisting of a 14E1 single-chain
(sc) Fv antibody fragment linked to human TNF-α retained TNF-α activity. This scFv(14E1)-TNF-α molecule localized specifically
to EGFR on the surface of tumor cells and activated the NF-κB pathway in co-cultured T cells, as demonstrated by electrophoretic
mobility shift assays.
Received: 6 May 1998 / Accepted: 16 July 1998 相似文献
15.
Sun CS Wu KT Lee HH Uen YH Tian YF Tzeng CC Wang AH Cheng CJ Tsai SL 《Journal of biomedical science》2008,15(5):633-643
The link of proto-oncogenic protein Wnt-1 production with NF-κB activation has been functionally demonstrated in PC12 cells, a rat pheochromocytoma cell line of neural
crest lineage, while it is not yet verified in human cells. The link can be indirectly supported in our previous report that
functional proteomics identifies enhanced expression of NF-κB-associated Wnt-1 production in human hepatocellular carcinoma tissues. This study aimed to further validate this link in human cells using
anti-sense strategy. The effects of sequence-specific anti-sense morpholino oligonucleotides (ONs) targeting against pre-mRNA
sequences of human p50 and p65 subunits of NF-κB as well as Wnt-1 genes were investigated. It revealed that all the three morpholino ONs inhibited NF-κB activation in human hepatoblastoma
cell line HepG2 cells along with decreased Wnt-1 production. Chromatin immunoprecipitation assay ascertained the direct binding of NF-κB-p50 to the Wnt-1 promoter. Additionally, anti-P50 and anti-P65 morpholino ONs also repressed the phosphorylation of Iκ Bα which temporarily
correlated with the inhibition of NF-κB activation accompanied by decreased Wnt-1 production by HepG2 cells. In summary, NF-κB activation is critically involved in the production of Wnt-1 by HepG2 cells. These results may have important oncology implications in treating patients with NF-κB-associated Wnt-1-producing cancers.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
16.
Jung Ha Kim Kabsun Kim Hye Mi Jin Insun Song Bang Ung Youn Junwon Lee Nacksung Kim 《Molecules and cells》2009,28(3):201-207
Silibinin is a polyphenolic flavonoid compound isolated from milk thistle (Silybum marianum), with known hepatoprotective, anticarcinogenic, and antioxidant effects. Herein, we show that silibinin inhibits receptor
activator of NF-κB ligand (RANKL)-induced osteoclastogenesis from RAW264.7 cells as well as from bone marrow-derived monocyte/macrophage
cells in a dose-dependent manner. Silibinin has no effect on the expression of RANKL or the soluble RANKL decoy receptor osteoprotegerin
(OPG) in osteoblasts. However, we demonstrate that silibinin can block the activation of NF-κB, c-Jun N-terminal kinase (JNK),
p38 mitogen-activated protein (MAP) kinase, and extracellular signal-regulated kinase (ERK) in osteoclast precursors in response
to RANKL. Furthermore, silibinin attenuates the induction of nuclear factor of activated T cells (NFAT) c1 and osteoclast-associated
receptor (OSCAR) expression during RANKL-induced osteoclastogenesis. We demonstrate that silibinin can inhibit TNF-α-induced
osteoclastogenesis as well as the expression of NFATc1 and OSCAR. Taken together, our results indicate that silibinin has
the potential to inhibit osteoclast formation by attenuating the downstream signaling cascades associated with RANKL and TNF-α. 相似文献
17.
Rainer Voisard Nicola Huber Regine Baur Milorat Susa Oliver Ickrath Anton Both Wolfgang Koenig Vinzenz Hombach 《BMC molecular biology》2001,2(1):7-7
Background
Activation of nuclear factor-κB (NF-κB) is one of the key events in early atherosclerosis and restenosis. We hypothesized that tumor necrosis factor-α (TNF-α) induced and NF-κB mediated expression of intercellular adhesion molecule-1 (ICAM-1) can be inhibited by antisense RelA p65 and NF-κB1 p50 oligonucleotides (RelA p65 and NF-κB1 p50). 相似文献18.
19.