Anti-inflammatory agents inhibit the induction of leptin by tumor necrosis factor-α

2002 ◽  
Vol 282 (5) ◽  
pp. R1429-R1435 ◽  
Author(s):  
Brian N. Finck ◽  
Rodney W. Johnson
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Epididymal Adipose Tissue ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Leptin Expression ◽  
Necrosis Factor

Tumor necrosis factor (TNF)-α stimulates the secretion of the adipocyte-derived hormone leptin. However, the cellular mechanisms by which TNF-α influences leptin production are poorly understood. To examine this issue, epididymal fat pads were isolated from mice and cultured in recombinant murine TNF-α (100 ng/ml). Compared with medium-treated controls, steady-state leptin expression was increased in TNF-α-treated explants. Culture with inhibitors of translation (cycloheximide) or transcription (actinomycin-D) abrogated the induction of leptin following TNF-α. Explants were also cultured in the presence of the anti-inflammatory p38 mitogen-activated protein kinase inhibitor (SB-203580) or PG J2 metabolite [15-deoxy-Δ12,14-PG J2 (PGJ)] and then exposed to TNF-α. Both compounds completely abolished TNF-α-induced increases in leptin production. To test the relevance of this in vivo, mice were pretreated with PGJ and then given TNF-α. PGJ treatment markedly blunted the TNF-α-induced increase in leptin, TNF-α, and interleukin-6 gene expression in epididymal adipose tissue. Collectively, these data indicate that TNF-α acutely activates leptin expression and that anti-inflammatory agents can abrogate TNF-α-induced hyperleptinemia.

scholarly journals Anti-Inflammatory and Anti-Allergic Effects of Saponarin and Its Impact on Signaling Pathways of RAW 264.7, RBL-2H3 and HaCaT Cells

2021 ◽  
Vol 22 (16) ◽  
pp. 8431
Author(s):  
Seon-Young Min ◽  
Che-Hwon Park ◽  
Hye-Won Yu ◽  
Young-Jin Park
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Skin Diseases ◽  
Mitogen Activated Protein Kinase ◽  
Hacat Cells ◽  
Protective Effects ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Necrosis Factor

Saponarin{5-hydroxy-2-(4-hydroxyphenyl)-6-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-7-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one}, a flavone found in young green barley leaves, is known to possess antioxidant, antidiabetic, and hepatoprotective effects. In the present study, the anti-inflammatory, anti-allergic, and skin-protective effects of saponarin were investigated to evaluate its usefulness as a functional ingredient in cosmetics. In lipopolysaccharide-induced RAW264.7 (murine macrophage) cells, saponarin (80 μM) significantly inhibited cytokine expression, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, inducible nitric oxide synthase, and cyclooxygenase (COX)-2. Saponarin (80 μM) also inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 involved in the mitogen-activated protein kinase signaling pathway in RAW264.7 cells. Saponarin (40 μM) significantly inhibited β-hexosaminidase degranulation as well as the phosphorylation of signaling effectors (Syk, phospholipase Cγ1, ERK, JNK, and p38) and the expression of inflammatory mediators (tumor necrosis factor [TNF]-α, IL-4, IL-5, IL-6, IL-13, COX-2, and FcεRIα/γ) in DNP-IgE- and DNP-BSA-stimulated RBL-2H3 (rat basophilic leukemia) cells. In addition, saponarin (100 μM) significantly inhibited the expression of macrophage-derived chemokine, thymus and activation-regulated chemokine, IL-33, thymic stromal lymphopoietin, and the phosphorylation of signaling molecules (ERK, p38 and signal transducer and activator of transcription 1 [STAT1]) in TNF-α- and interferon (IFN)-γ-stimulated HaCaT (human immortalized keratinocyte) cells. Saponarin (100 μM) also significantly induced the expression of hyaluronan synthase-3, aquaporin 3, and cathelicidin antimicrobial peptide (LL-37) in HaCaT cells, which play an important role as skin barriers. Saponarin remarkably inhibited the essential factors involved in the inflammatory and allergic responses of RAW264.7, RBL-2H3, and HaCaT cells, and induced the expression of factors that function as physical and chemical skin barriers in HaCaT cells. Therefore, saponarin could potentially be used to prevent and relieve immune-related skin diseases, including atopic dermatitis.

scholarly journals HSP70 Induction by ING Proteins Sensitizes Cells to Tumor Necrosis Factor Alpha Receptor-Mediated Apoptosis

2006 ◽  
Vol 26 (24) ◽  
pp. 9244-9255 ◽  
Author(s):  
Xiaolan Feng ◽  
Shirin Bonni ◽  
Karl Riabowol
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Kinase Inhibitor ◽  
Heat Shock Gene ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Primary Fibroblasts ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT ING proteins affect apoptosis, growth, and DNA repair by transducing stress signals such as DNA damage, binding histones, and subsequently regulating chromatin structure and p53 activity. p53 target genes, including the p21 cyclin-dependent kinase inhibitor and Bax, an inducer of apoptosis, are regulated by ING proteins. To identify additional targets downstream of p33ING1 and p32ING2, cDNA microarrays were performed on phenotypically normal human primary fibroblasts. The 0.36% of genes affected by ING proteins in primary fibroblasts were distinct from targets seen in established cells and included the HSP70 heat shock gene, whose promoter was specifically induced >10-fold. ING1-induced expression of HSP70 shifted cells from survival to a death pathway in response to tumor necrosis factor alpha (TNF-α), and p33ING1b protein showed synergy with TNF-α in inducing apoptosis, which correlated with reduced NF-κB-dependent transcription. These findings are consistent with previous reports that HSP70 promotes TNF-α-mediated apoptosis by binding I-κΒ kinase gamma and impairing NF-κB survival signaling. Induction of HSP70 required the amino terminus of ING1b but not the plant homeodomain region that was recently identified as a histone binding domain. Regulation of HSP70 gene expression by the ING tumor suppressors provides a novel link between the INGs and the stress-regulated NF-κB survival pathway important in hypoxia and angiogenesis.

scholarly journals Repetitive Injections of Dendritic Cells Matured with Tumor Necrosis Factor α Induce Antigen-specific Protection of Mice from Autoimmunity

2001 ◽  
Vol 195 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Mauritius Menges ◽  
Susanne Rößner ◽  
Constanze Voigtländer ◽  
Heike Schindler ◽  
Nicole A. Kukutsch ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cell Immunity ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Mature dendritic cells (DCs) are believed to induce T cell immunity, whereas immature DCs induce T cell tolerance. Here we describe that injections of DCs matured with tumor necrosis factor (TNF)-α (TNF/DCs) induce antigen-specific protection from experimental autoimmune encephalomyelitis (EAE) in mice. Maturation by TNF-α induced high levels of major histocompatibility complex class II and costimulatory molecules on DCs, but they remained weak producers of proinflammatory cytokines. One injection of such TNF/DCs pulsed with auto-antigenic peptide ameliorated the disease score of EAE. This could not be observed with immature DCs or DCs matured with lipopolysaccharide (LPS) plus anti-CD40. Three consecutive injections of peptide-pulsed TNF/DCs derived from wild-type led to the induction of peptide-specific predominantly interleukin (IL)-10–producing CD4+ T cells and complete protection from EAE. Blocking of IL-10 in vivo could only partially restore the susceptibility to EAE, suggesting an important but not exclusive role of IL-10 for EAE prevention. Notably, the protection was peptide specific, as TNF/DCs pulsed with unrelated peptide could not prevent EAE. In conclusion, this study describes that stimulation by TNF-α results in incompletely matured DCs (semi-mature DCs) which induce peptide-specific IL-10–producing T cells in vivo and prevent EAE.

scholarly journals EVALUATION OF AQUEOUS FRUIT EXTRACT OF TAMARINDUS INDICA (L) FOR INHIBITION OF TUMOR NECROSIS FACTOR-a AND CYCLO OXYGENASE ENZYMES IN EXPERIMENTAL ANIMAL

2018 ◽  
Vol 11 (3) ◽  
pp. 57 ◽  
Author(s):  
Mohammad Daud Ali ◽  
Atul Kumar Gupta ◽  
Arif Naseer ◽  
Mohd Aamir Mirza ◽  
Sabir Afzal
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Significant Inhibition ◽  
Tamarindus Indica ◽  
Screening Assay ◽  
Standard Drug ◽  
Cox Inhibitor ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Necrosis Factor

 Objective: The main objective of this study was to assess tumor necrosis factor-α (TNF)-α and cyclooxygenase enzymes (COX) inhibition potency of Tamarindus indica Linn. in comparison to standard drug (indomethacin).Methods: Three plants are selected for the studies, namely: Aloe vera (L.), Terminalia chebula Reitz., and T. indica Linn. Estimation of TNF-α in serum (at 1:10 dilution in PBS) was performed using the immunoenzymatic (ELISA) technique. COX inhibitor screening assay kits were used for estimation of COX.Result: All three plant extracts showed a potent significant inhibition of the COX enzyme as compared to the positive control and standard drug when the animal was administered with 400 mg/kg. These studies indicate that the T. indica plant extract showed significant COX inhibition even at low dose. All the extracts were effective anti-inflammatory in nature, however, T. indica extracts at a dose of 400 mg/kg were found to be most potent. It was found to be comparable with that of Indomethacin 10 mg/kg body weight.Conclusion: The anti-inflammatory activity expressed by all the three plants A. vera (L.), T. chebula Reitz., and T. indica L. Among all three plants T. indica (L) was found to be more active against both TNF-α and COX, and it was comparable to standard drug Indomethacin. Need further studies to elucidate the exact secondary metabolite by which these plants express this activity.

scholarly journals Modification of Tumor Necrosis Factor-α and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot Syndrome

Biology ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 3
Author(s):  
Karine O. Galstyan ◽  
Ludmila V. Nedosugova ◽  
Narine S. Martirosian ◽  
Nikita G. Nikiforov ◽  
Natalia V. Elizova ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Diabetic Foot ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Tnf Α ◽  
Inflammatory Activation ◽  
Chemokine Ligand ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor

Background: This study involves the investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory chemokine C-C motif chemokine ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers. Methods: A total of 121 patients with T2DM (79 without diabetic foot syndrome (DFS) and 42 patients with DFS) were included. Cluster of Differentiation 14 (CD14+) monocytes were isolated from patients’ blood and stimulated by interferon-γ (IFN-γ) and interleukin-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF-α and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation. Results: We found a correlation between glycated hemoglobin (HbA1c) and stimulated secretion levels of TNF-α (r = 0.726, p = 0.027) and CCL18 (r = –0.949, p = 0.051) in patients with DFS. There was an increase of pro- and anti-inflammatory activation of monocytes in all patients with different durations of DFS (p < 0.05). However, no stimulation of anti-inflammatory activation was detected in patients with DFS lasting more than 6 months (p = 0.033). Conclusions: Our study showed an increase in pro-inflammatory secretion and a decrease in anti-inflammatory secretion by monocytes isolated from blood of patients with T2DM depending on HbA1c levels and duration of the inflammatory process. These findings allow us to assume that monocytes isolated from T2DM patients are characterized by a biased ability to respond towards pro-inflammatory stimulation, contributing to the chronic wound process.

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 The Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinases MK2 and MK3 Cooperate in Stimulation of Tumor Necrosis Factor Biosynthesis and Stabilization of p38 MAPK

2006 ◽  
Vol 27 (1) ◽  
pp. 170-181 ◽  
Author(s):  
N. Ronkina ◽  
A. Kotlyarov ◽  
O. Dittrich-Breiholz ◽  
M. Kracht ◽  
E. Hitti ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Tumor Necrosis Factor ◽  
Protein Kinases ◽  
Tumor Necrosis ◽  
Mitogen Activated Protein Kinase ◽  
Double Knockout ◽  
Mitogen Activated Protein ◽  
Deficient Mice ◽  
Necrosis Factor

ABSTRACT MK2 and MK3 represent protein kinases downstream of p38 mitogen-activated protein kinase (MAPK). Deletion of the MK2 gene in mice resulted in an impaired inflammatory response although MK3, which displays extensive structural similarities and identical functional properties in vitro, is still present. Here, we analyze tumor necrosis factor (TNF) production and expression of p38 MAPK and tristetraprolin (TTP) in MK3-deficient mice and demonstrate that there are no significant differences with wild-type animals. We show that in vivo MK2 and MK3 are expressed and activated in parallel. However, the level of activity of MK2 is always significantly higher than that of MK3. Accordingly, we hypothesized that MK3 could have significant effects only in an MK2-free background and generated MK2/MK3 double-knockout mice. Unexpectedly, these mice are viable and show no obvious defects due to loss of compensation between MK2 and MK3. However, there is a further reduction of TNF production and expression of p38 and TTP in double-knockout mice compared to MK2-deficient mice. This finding, together with the observation that ectopically expressed MK3 can rescue MK2 deficiency similarly to MK2, indicates that both kinases share the same physiological function in vivo but are expressed to different levels.

scholarly journals Apigenin-7-Glucuronide from Urera aurantiaca Inhibits Tumor Necrosis Factor Alpha and Total Nitrite Release in Lipopolysaccharide-Activated Macrophages

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Carla Marrassini ◽  
Laura Cogoi ◽  
Valeria Sülsen ◽  
Claudia Anesini
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Maximum Effect ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor ◽  
Inflammatory Effect

Urera aurantiaca is an Argentinean medicinal and edible species traditionally used to treat symptoms of inflammation. The aim of this study was to evaluate the anti-inflammatory activity of a methanol extract and its major compound. U. aurantiaca aerial parts were extracted with methanol by maceration. A phytochemical analysis was performed, and the extract’s major component, apigenin-7-glucuronide (A7G), was identified by spectroscopic and HPLC methods. The analysis of the inflammatory mediators nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) in lipopolysaccharide- (LPS-) stimulated macrophages were used in the evaluation of the extract and the major compound anti-inflammatory effects. The extract reduced LPS-augmented NO release from 100 μg/mL (27%), reaching the highest inhibition at 1000 μg/mL (96.3%), while A7G reduced it 30.7% at 1 μg/mL, and its maximum effect was 97.1% at 10 μg/mL. In the TNF-α model, the extract at 500 and 1000 μg/mL reduced LPS-augmented TNF-α by 13.5% and 93.9%, respectively; meanwhile, A7G reduced it by 26.2% and 83.8% at 5 and 10 μg/mL, respectively. U. aurantiaca popular use was validated. In the present study, for the first time, A7G was isolated from U. aurantiaca; furthermore, A7G showed anti-inflammatory effect in the macrophage cell line RAW264.7 (ATCC) and seems to be responsible for the extract anti-inflammatory effect.

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