Dynamic change of TNIK in response to tumor necrosis factor alpha in a TRAF2-dependent manner

Human Cell ◽  
2013 ◽  
Vol 26 (2) ◽  
pp. 67-72 ◽  
Author(s):  
Jinghua Gui ◽  
Zhenhai Li ◽  
Xiumei Zhou
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Dynamic Change ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

scholarly journals Bikunin Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Induction in Macrophages

2004 ◽  
Vol 11 (6) ◽  
pp. 1140-1147 ◽  
Author(s):  
Hidenori Matsuzaki ◽  
Hiroshi Kobayashi ◽  
Tatsuo Yagyu ◽  
Kiyoshi Wakahara ◽  
Toshiharu Kondo ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Dose Dependent ◽  
Necrosis Factor

ABSTRACT Bikunin, a Kunitz-type protease inhibitor, exhibits anti-inflammatory activity in protection against cancer and inflammation. To investigate the molecular mechanism of this inhibition, we analyzed the effect of bikunin on tumor necrosis factor alpha (TNF-α) production in human peripheral mononuclear cells stimulated by lipopolysaccharide (LPS), an inflammatory inducer. Here, we show the following results. (i) LPS induced TNF-α expression in time- and dose-dependent manners through phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase pathways. (ii) Bikunin inhibits LPS-induced up-regulation of TNF-α protein expression in a dose-dependent manner, reaching 60% inhibition at the highest doses of bikunin tested (5.0 μM). (iii) Inhibition by bikunin of TNF-α induction correlates with the suppressive capacity of ERK1/2, JNK, and p38 signaling pathways, implicating repressions of at least three different signals in the inhibition. (iv) Bikunin blocks the induction of TNF-α target molecules interleukin-1β (IL-1β) and IL-6 proteins. (v) Bikunin is functional in vivo, and this glycoprotein blocks systemic TNF-α release in mice challenged with LPS. (vi) Finally, bikunin can prevent LPS-induced lethality. In conclusion, bikunin significantly inhibits LPS-induced TNF-α production, suggesting a mechanism of anti-inflammation by bikunin through control of cytokine induction during inflammation. Bikunin might be a candidate for the treatment of inflammation, including septic shock.

scholarly journals Ectodomain Shedding of Preadipocyte Factor 1 (Pref-1) by Tumor Necrosis Factor Alpha Converting Enzyme (TACE) and Inhibition of Adipocyte Differentiation

2006 ◽  
Vol 26 (14) ◽  
pp. 5421-5435 ◽  
Author(s):  
Yuhui Wang ◽  
Hei Sook Sul
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Adipocyte Differentiation ◽  
Soluble Form ◽  
Dependent Manner ◽  
Converting Enzyme ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Preadipocyte factor 1 (Pref-1), an epidermal growth factor repeat containing transmembrane protein found in the preadipocytes, inhibits adipocyte differentiation in vitro and in vivo. Here, we examined the processing of membrane form of Pref-1A to release the 50-kDa soluble form that inhibits adipocyte differentiation. The ectodomain cleavage of Pref-1 is markedly enhanced by phorbol 12-myristate 13-acetate in a dose- and time-dependent manner. The basal and stimulated cleavage is inhibited by the broad metalloproteinase inhibitor GM6001, a fact that suggests that cleavage of membrane Pref-1A is dependent on a metalloproteinase. Next, we showed that release of soluble Pref-1A is inhibited by TAPI-0 and by a tissue inhibitor of metalloproteinase-3, TIMP-3, that can inhibit tumor necrosis factor alpha converting enzyme (TACE), but not by TIMP-1 or TIMP-2. On the other hand, overexpression of TACE increases Pref-1 cleavage to produce the 50-kDa soluble form. Furthermore, this cleavage was not detected in cells with TACE mutation or with TACE small interfering RNA. TACE-mediated shedding of Pref-1 ectodomain inhibits adipocyte differentiation of 3T3-L1 cells and in Pref-1-null mouse embryo fibroblasts transduced with Pref-1A. Identification of TACE as the major protease responsible for conversion of membrane-bound Pref-1 to the biologically active diffusible form provides a new insight into Pref-1 function in adipocyte differentiation.

scholarly journals Tumor Necrosis Factor Alpha Induction of NF-κB Requires the Novel Coactivator SIMPL

2004 ◽  
Vol 24 (21) ◽  
pp. 9317-9326 ◽  
Author(s):  
Hyung-Joo Kwon ◽  
Erin Haag Breese ◽  
Eva Vig-Varga ◽  
Yong Luo ◽  
Younghee Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Type I ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT A myriad of stimuli including proinflammatory cytokines, viruses, and chemical and mechanical insults activate a kinase complex composed of IκB kinase β (IKK-β), IKK-α, and IKK-γ/N, leading to changes in NF-κB-dependent gene expression. However, it is not clear how the NF-κB response is tailored to specific cellular insults. Signaling molecule that interacts with mouse pelle-like kinase (SIMPL) is a signaling component required for tumor necrosis factor alpha (TNF-α)-dependent but not interleukin-1-dependent NF-κB activation. Herein we demonstrate that nuclear localization of SIMPL is required for type I TNF receptor-induced NF-κB activity. SIMPL interacts with nuclear p65 in a TNF-α-dependent manner to promote endogenous NF-κB-dependent gene expression. The interaction between SIMPL and p65 enhances p65 transactivation activity. These data support a model in which TNF-α activation of NF-κB dependent-gene expression requires nuclear relocalization of p65 as well as nuclear relocalization of SIMPL, generating a TNF-α-specific induction of gene expression.

scholarly journals Glucocorticoids Regulate Tristetraprolin Synthesis and Posttranscriptionally Regulate Tumor Necrosis Factor Alpha Inflammatory Signaling

2006 ◽  
Vol 26 (23) ◽  
pp. 9126-9135 ◽  
Author(s):  
Kathleen Smoak ◽  
John A. Cidlowski
Keyword(s):  
Tumor Necrosis Factor ◽  
Mrna Expression ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Dependent Manner ◽  
Inflammatory Signaling ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Glucocorticoids are used to treat various inflammatory disorders, but the mechanisms underlying these actions are incompletely understood. The zinc finger protein tristetraprolin (TTP) destabilizes several proinflammatory cytokine mRNAs by binding to AU-rich elements within their 3′ untranslated regions, targeting them for degradation. Here we report that glucocorticoids induce the synthesis of TTP mRNA and protein in A549 lung epithelial cells and in rat tissues. Dexamethasone treatment leads to a sustained induction of TTP mRNA expression that is abrogated by RU486. Glucocorticoid induction of TTP mRNA is also blocked by actinomycin D but not by cycloheximide, suggesting a transcriptional mechanism which has been confirmed by transcription run-on experiments. The most widely characterized TTP-regulated gene is the AU-rich tumor necrosis factor alpha (TNF-α) gene. Dexamethasone represses TNF-α mRNA in A549 cells and decreases luciferase expression of a TNF-α 3′ untranslated region reporter plasmid in an orientation-dependent manner. Small interfering RNAs to TTP significantly prevent this effect, and a cell line stably expressing a short-hairpin RNA to TTP conclusively establishes that TTP is critical for dexamethasone inhibition of TNF-α mRNA expression. These studies provide the molecular evidence for glucocorticoid regulation of human TTP and reflect a novel inductive anti-inflammatory signaling pathway for glucocorticoids that acts via posttranscriptional mechanisms.

Erythromycin Inhibition of Lipopolysaccharide-Stimulated Tumor Necrosis Factor Alpha Production by Human Monocytes in Vitro

1992 ◽  
Vol 101 (10_suppl) ◽  
pp. 16-20 ◽  
Author(s):  
Yukiko Iino ◽  
Minoru Toriyama ◽  
Yasuhiro Natori ◽  
Koichiro Kudo ◽  
Akira Yuo
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Penicillin G ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

The mechanism of clinical effectiveness of low-dose and long-term erythromycin (EM) treatment for diffuse panbronchiolitis, sinobronchial syndrome, and associated otitis media with effusion was investigated by studying the effects of EM on tumor necrosis factor alpha (TNF-α) production by cultured human monocytes stimulated with lipopolysaccharide. At concentrations of 0.1 μg/mL or more, EM inhibited TNF-α release from human monocytes stimulated by lipopolysaccharide in a dose-dependent manner. Of the other macrolides tested, roxithromycin, an EM derivative, also showed significant inhibition of TNF-α production, whereas josamycin failed to inhibit TNF-α release from monocytes. Nonmacrolidic drugs such as minocycline hydrochloride, ofloxacin, or penicillin G had no significant effect on TNF-α production. These results suggest that the clinical improvement of chronic respiratory diseases by EM may depend on the suppression of production of inflammatory cytokines such as TNF-α.

scholarly journals Sitafloxacin reduces tumor necrosis factor alpha (TNFα) converting enzyme (TACE) phosphorylation and activity to inhibit TNFα release from lipopolysaccharide-stimulated THP-1 cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ippei Sakamaki ◽  
Michika Fukushi ◽  
Wakana Ohashi ◽  
Yukie Tanaka ◽  
Kazuhiro Itoh ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Systemic Reaction ◽  
Dependent Manner ◽  
Converting Enzyme ◽  
Necrosis Factor Alpha ◽  
Quinolone Antibiotics ◽  
Factor Alpha ◽  
Necrosis Factor

AbstractSepsis is a systemic reaction to an infection and resulting in excessive production of inflammatory cytokines and chemokines. It sometimes results in septic shock. The present study aimed to identify quinolone antibiotics that can reduce tumor necrosis factor alpha (TNFα) production and to elucidate mechanisms underlying inhibition of TNFα production. We identified quinolone antibiotics reduced TNFα production in lipopolysaccharide (LPS)-stimulated THP-1 cells. Sitafloxacin (STFX) is a broad-spectrum antibiotic of the quinolone class. STFX effectively suppressed TNFα production in LPS-stimulated THP-1 cells in a dose-dependent manner and increased extracellular signal-regulated kinase (ERK) phosphorylation. The percentage of intracellular TNFα increased in LPS-stimulated cells with STFX compared with that in LPS-stimulated cells. TNFα converting enzyme (TACE) released TNFα from the cells, and STFX suppressed TACE phosphorylation and activity. To conclude, one of the mechanisms underlying inhibition of TNFα production in LPS-stimulated THP-1 cells treated with STFX is the inhibition of TNFα release from cells via the suppression of TACE phosphorylation and activity. STFX may kill bacteria and suppress inflammation. Therefore, it can be effective for sepsis treatment.

Pleural mesothelial cell response to inflammation: tumor necrosis factor-induced mitogenesis and collagen synthesis

1993 ◽  
Vol 265 (4) ◽  
pp. L382-L388 ◽  
Author(s):  
M. W. Owens ◽  
S. R. Grimes
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Collagen Synthesis ◽  
Mesothelial Cell ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Dose Dependent ◽  
Necrosis Factor

This study examined the effects of tumor necrosis factor-alpha on pleural mesothelial cell proliferation and collagen synthesis, functions which may be important in the response of the pleura to injury. Tumor necrosis factor-alpha caused a significant increase in proliferation and collagen production by rat pleural mesothelial cells in vitro. Proliferation increased in a time- and dose-dependent manner, resulting in an approximate twofold increase in the uptake of [3H]thymidine relative to control. The uptake of [3H]proline into collagenase-sensitive protein increased in a dose-dependent manner for concentrations of tumor necrosis factor-alpha > or = 1.0 ng/ml. The increase in collagen production were associated with increased steady-state levels of alpha 1(I)-procollagen mRNA. These results suggest that tumor necrosis factor-alpha may have a significant effect on pleural mesothelial cell function in vivo in the setting of inflammation. Increases in pleural mesothelial cell proliferation and collagen synthesis in response to inflammatory mediators, like tumor necrosis factor-alpha, may be important in healing the pleura after injury by a variety of disease processes.

scholarly journals LARP4 Is Regulated by Tumor Necrosis Factor Alpha in a Tristetraprolin-Dependent Manner

2015 ◽  
Vol 36 (4) ◽  
pp. 574-584 ◽  
Author(s):  
Sandy Mattijssen ◽  
Richard J. Maraia
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Rna Binding ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Transient Decrease ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

LARP4 is a protein with unknown function that independently binds to poly(A) RNA, RACK1, and the poly(A)-binding protein (PABPC1). Here, we report on its regulation. We found a conserved AU-rich element (ARE) in the human LARP4 mRNA 3′ untranslated region (UTR). This ARE, but not its antisense version or a point-mutated version, significantly decreased the stability of β-globin reporter mRNA. We found that overexpression of tristetraprolin (TTP), but not its RNA binding mutant or the other ARE-binding proteins tested, decreased cellular LARP4 levels. RNA coimmunoprecipitation showed that TTP specifically associated with LARP4 mRNAin vivo. Consistent with this, mouse LARP4 accumulated to higher levels in TTP gene knockout (KO) cells than in control cells. Stimulation of WT cells with tumor necrosis factor alpha (TNF-α), which rapidly induces TTP, robustly decreased LARP4 with a coincident time course but had no such effect on LARP4B or La protein or on LARP4 in the TTP KO cells. The TNF-α-induced TTP pulse was followed by a transient decrease in LARP4 mRNA that was quickly followed by a subsequent transient decrease in LARP4 protein. Involvement of LARP4 as a target of TNF-α–TTP regulation provides a clue as to how its functional activity may be used in a physiologic pathway.

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