Epigallocatechin Gallate Modulates Cytokine Production by Bone Marrow-Derived Dendritic Cells Stimulated with Lipopolysaccharide or Muramyldipeptide, or Infected with Legionella pneumophila

2005 ◽  
Vol 230 (9) ◽  
pp. 645-651 ◽  
Author(s):  
James Rogers ◽  
Izabella Perkins ◽  
Alberto van Olphen ◽  
Nicholas Burdash ◽  
Thomas W. Klein ◽  
...  
Keyword(s):  
Legionella Pneumophila ◽  
Tumor Necrosis ◽  
Epigallocatechin Gallate ◽  
Dependent Manner ◽  
Enhanced Production ◽  
Tnf Α ◽  
Factor Α ◽  
Dose Dependent ◽  
Antimicrobial Immunity ◽  
Necrosis Factor

The primary polyphenol in green tea extract is the catechin epigallocatechin gallate (EGCG). Various studies have shown significant suppressive effects of catechin on mammalian cells, either tumor or normal cells, including lymphoid cells. Previous studies from this laboratory reported that EGCG has marked suppressive activity on murine macrophages infected with the intracellular bacterium Legionella pneumophila (Lp), an effect mediated by enhanced production of both tumor necrosis factor-α (TNF-α) and γ-interferon (IFN-γ). In the present study, primary murine bone marrow (BM)-derived dendritic cells (DCs), a phagocytic monocytic cell essential for innate immunity to intracellular microorganisms, such as Lp, were stimulated in vitro with the microbial stimulant lipopolysaccharide (LPS) from gram-negative bacteria, the cell wall component from gram-positive bacteria muramyldipeptide (MDP) or infected with Lp. Production of the T helper cell (Th1)-activating cytokine, interleukin-12 (IL-12) and the proinflammatory cytokine, tumor necrosis factor-α (TNF-α), produced mainly by phagocytic cells and important for antimicrobial immunity, was determined in cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). Treatment of the cells with EGCG inhibited, in a dose-dependent manner, production of IL-12. In contrast, enhanced production of TNF-α occurred in a dose-dependent manner in the DC cultures stimulated with either soluble bacterial product or infected with Lp. Thus, the results of this study show that the EGCG catechin has a marked effect in modulating production of these immunoregulatory cytokines in stimulated DCs, which are important for antimicrobial immunity, especially innate immunity. Further studies are necessary to characterize the physiologic function of the effect of EGCG on TNF-α and IL-12 during Lp infection, and the mechanisms involved.

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.

Anti-inflammatory Activity of Herbal Medicines: Inhibition of Nitric Oxide Production and Tumor Necrosis Factor-α Secretion in an Activated Macrophage-like Cell Line

2005 ◽  
Vol 33 (03) ◽  
pp. 415-424 ◽  
Author(s):  
Eunkyue Park ◽  
Susan Kum ◽  
Chuanhua Wang ◽  
Seung Yong Park ◽  
Bo Sook Kim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis ◽  
No Production ◽  
Dependent Manner ◽  
Aqueous Extracts ◽  
Tnf Α ◽  
Activated Macrophage ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Necrosis Factor

Houttuynia cordata Thunb. (HC), Glycyrrhiza uralensis Fischer (GU), Forsythia suspense (Thunb.) Vahl (FS), and Lonicera japonica Thunb. (LJ) are Chinese herbs known to possess anti-inflammatory properties. The effects of aqueous extracts of these herbs on the production of the pro-inflammatory mediators, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) were examined in an activated macrophage-like cell line, RAW 264.7 cells. Aqueous extracts from FS at 0.0625–2.0 mg/ml inhibited in vitro production of NO and secretion of TNF-α in a dose-dependent manner. FS at 1.0–2.0 mg/ml and 0.125–2.0 mg/ml significantly inhibited NO production and TNF-α, respectively. An extract of LJ demonstrated potent inhibition of both NO production and TNF-α secretion in a dose-dependent manner. An aqueous extract from HC inhibited NO production in a dose-dependent manner, but minimally (approximately 30%) inhibited TNF-α secretion at 0.0625 and 0.125 mg/ml. In contrast, an aqueous extract of GU had a minimal effect on both the production of NO and the secretion of TNF-α. Viability of cells at all concentrations studied was unaffected as determined by MTT cytotoxicity assay and trypan blue dye exclusion. These results suggest that aqueous extracts from FS, LJ and HC have anti-inflammatory actions as measured by inhibition of NO production and/or TNF-α secretion.

scholarly journals Extracts of Thai Perilla frutescens nutlets attenuate tumour necrosis factor-α-activated generation of microparticles, ICAM-1 and IL-6 in human endothelial cells

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Narisara Paradee ◽  
Niramon Utama-ang ◽  
Chairat Uthaipibull ◽  
John B. Porter ◽  
Maciej W. Garbowski ◽  
...  
Keyword(s):  
Tumour Necrosis ◽  
Endothelial Activation ◽  
Perilla Frutescens ◽  
Dependent Manner ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Ea.Hy926 Cells ◽  
Factor Α ◽  
Dose Dependent ◽  
Necrosis Factor

Abstract Elevation of endothelial microparticles (EMPs) play an important role in the progression of inflammation-related vascular diseases such as cardiovascular diseases (CVDs). Thai perilla (Perilla frutescens) nutlets are rich in phenolic compounds and flavonoids that exert potent antioxidant and anti-inflammatory effects. We found that the ethyl acetate (EA) and ethanol (Eth) extracts of Thai perilla nutlets contain phenolic compounds such as luteolin, apigenin, chryseoriol and their glycosides, which exhibit antioxidant activity. The goal of the present study was to investigate the effects of the extracts on endothelial activation and EMPs generation in tumour necrosis factor-α (TNF-α)-induced EA.hy926 cells. We found that TNF-α (10 ng/ml) activated EA.hy926 cells and subsequently generated EMPs. Pre-treatment with the extracts significantly attenuated endothelial activation by decreasing the expression of the intracellular adhesion molecule-1 (ICAM-1) in a dose-dependent manner. Only the Eth extract showed protective effects against overproduction of interleukin-6 (IL-6) in the activated cells. Furthermore, the extracts significantly reduced TNF-α-enhanced EMPs generation in a dose-dependent manner. In conclusion, Thai perilla nutlet extracts, especially the Eth extract, may have potential to protect endothelium against vascular inflammation through the inhibition of endothelial activation and the generation of endothelial microparticles (EMPs).

Rat adipocyte apoptosis induced by TNF-α

2005 ◽  
Vol 2 (3) ◽  
pp. 149-153
Author(s):  
Lin Ya-Qiu ◽  
Li Rui-Wen ◽  
Sun Chao ◽  
Chen Guo-Zhu ◽  
Yang Yong-Qing ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Dependent Manner ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Apoptotic Effect ◽  
High Concentrations ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Dose Dependent ◽  
Necrosis Factor

AbstractThe effects of different concentrations of tumour necrosis factor-α (TNF-α) on rat adipocyte apoptosis were detected by optical microscopy, agarose gel electrophoresis and flow cytometry methods. The morphological changes of rat adipocyte apoptosis induced by TNF-α correlated linearly with the concentration of TNF-α, ranging from 5 to 20 ng/ml. High concentrations of TNF-α induced more obvious apoptosis. Significant morphological changes of rat adipocytes treated with 5 ng/ml TNF-α were noticed, but DNA ladders did not appear in the DNA electrophoresis analysis, i.e. morphological changes occurred earlier than the biochemical changes. TNF-α induced apoptosis in the rat adipocyte in a dose-dependent manner. The induced apoptotic effect of 5, 10, 15 and 20 ng/ml TNF-α was significantly different (P0.01), but the effect among 10, 15 and 20 ng/ml TNF-α treatments was not significantly different (P0.05). Thus the optimum concentration of TNF-α for inducing apoptosis was 10 ng/ml.

scholarly journals Immunological properties of human decidual macrophages – a possible role in intrauterine immunity

Reproduction ◽  
2005 ◽  
Vol 129 (5) ◽  
pp. 631-637 ◽  
Author(s):  
Uma Singh ◽  
Grant Nicholson ◽  
Britta C Urban ◽  
Ian L Sargent ◽  
Uday Kishore ◽  
...  
Keyword(s):  
Superoxide Radicals ◽  
Late Gestation ◽  
Dependent Manner ◽  
Defence Mechanisms ◽  
Tnf Α ◽  
Bacterial Lipopolysaccharides ◽  
Factor Α ◽  
Intrauterine Infections ◽  
Dose Dependent ◽  
Necrosis Factor

Our aim was to investigate the contribution of decidual macrophages, which constitute an important immune component of the decidua in late gestation, to intrauterine defence mechanisms. Using flow cytometry we examined the ability of decidual macrophages, isolated from term decidua, to bind and phagocytose fluorescence-labelled bacterial and yeast bioparticles. We also assessed their ability to generate superoxide radicals and tumour necrosis factor-α following lipopolysaccharide challenge. Decidual macrophages bound bacterial and yeast particles in a dose-dependent manner, which subsequently led to phagocytosis. These macrophages also produced superoxide radicals and the pro-inflammatory cytokine TNF-α when challenged with bacterial lipopolysaccharides. These results suggest a role for decidual macrophages in pathogen recognition and clearance during pregnancy, and, therefore, they are likely to protect the fetus against intrauterine infections which might otherwise lead to preterm labour.

Tumor necrosis factor-α decreases thyrotropin-induced 5′-deiodinase activity in FRTL-5 thyroid cells

1994 ◽  
Vol 130 (5) ◽  
pp. 502-507 ◽  
Author(s):  
Boonsong Ongphiphadhanakul ◽  
Shih Lieh Fang ◽  
Kam-Tsun Tang ◽  
Nilima A Patwardhan ◽  
Lewis E Braverman
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Dependent Manner ◽  
Thyroid Cells ◽  
Deiodinase Activity ◽  
Tnf Α ◽  
Rat Thyroid ◽  
Factor Α ◽  
Necrosis Factor

Ongphiphadhanakul B, Fang SL, Tang K-T, Patwardhan NA, Braverman LE. Tumor necrosis factor-α decreases thyrotropin-induced 5′-deiodinase activity in FRTL-5 thyroid cells. Eur J Endocrinol 1994;130:502–7. ISSN 0804–4643 Tumor necrosis factor-α (TNF-α) exerts various effects on many cell types. Acute administration of TNF-α to rats decreases hepatic 5′-deiodinase activity (5′D-I) and TNF-α has been implicated in the pathogenesis of the low triiodothyronine syndrome in non-thyroidal illness in humans. The thyroid, liver and kidney are rich in 5′D-I. Unlike hepatic and renal 5′D-I, thyroid 5′D-I is regulated by thyrotropin. We have investigated the effects of TNF-α on 5D-I in FRTL-5 cells, a cultured rat thyroid follicular cell line. Tumor necrosis factor-α did not significantly affect basal 5′D-I but thyrotropin markedly increased 5′D-I (p < 0.001). This TSH-induced increase in 5′D-I was attenuated by TNF-α in a dose-dependent manner (p < 0.001). Enzyme kinetic analysis demonstrated that thyrotropin increased 5′D-I by increasing Vmax (p < 0.01) without significantly affecting Km. Likewise, TNF-α decreased the thyrotropin-induced 5′D-I by decreasing Vmax (p < 0.05) but not Km. The effect of TNF-α on thyrotropin-induced 5′D-I in FRTL-5 cells is probably mediated through post-thyrotropin-induced generation of cyclic adenosine monophosphate (cAMP) because TNF-α inhibited both dibutyryl cAMP (p < 0.001) and forskolin (p < 0.001)-induced increases in 5′D-I without affecting cAMP generation stimulated by thyrotropin. In conclusion, we have demonstrated that TNF-α inhibits thyrotropininduced 5′D-I activity in FRTL-5 cells by pathways distal to the generation of cAMP and that TNF-α may play a role in the modulation of the production of triiodothyronine by the thyroid gland. Furthermore, the increase in TNF-α observed in patients with the euthyroid sick syndrome may contribute to the low serum triiodothyronine observed in these patients, not only by inhibiting peripheral generation of triiodothyronine from thyroxine but also by decreasing thyroidal generation and subsequent secretion of triiodothyronine. Lewis E Braverman, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA

scholarly journals Paeoniflorin Antagonizes TNF-α-Induced L929 Fibroblastoma Cells Apoptosis by Inhibiting NF-κBp65 Activation

Dose-Response ◽  
2018 ◽  
Vol 16 (2) ◽  
pp. 155932581877497 ◽  
Author(s):  
Xiaoyu Lai ◽  
Jing Wei ◽  
Xinghong Ding
Keyword(s):  
Dependent Manner ◽  
L929 Cells ◽  
Tnf Α ◽  
Flow Cytometry Detection ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Dose Dependent ◽  
Necrosis Factor ◽  
Inflammatory Effect

Paeoniflorin (PF) is one of the main pharmacodynamic components of Paeonia suffruticosa Andr, which has a significant anti-inflammatory effect on rheumatoid arthritis (RA), with a mechanism related to the tumor necrosis factor α (TNF-α). The aim of the present study was to investigate the role of PF in the apoptosis and expression of NF-κBp65 of L929 fibroblastoma cells induced by TNF-α. Our results showed that different concentrations of PF can significantly reduce the growth inhibition of L929 cells. Moreover, morphological observations, Hoechst 33342 staining, and flow cytometry detection of apoptosis showed that PF can significantly attenuate the TNF-α-induced apoptosis in a dose-dependent manner. Western blot analysis revealed that TNF-α induced the activation of NF-κBp65, whereas PF treatment had a marked dose-dependent suppression on it, which indicates that its action might be associated with inhibiting NF-κB signaling pathway. These results show that PF exerts a beneficial effect on L929 cells to prevent TNF-α-induced apoptosis and expression of NF-κBp65, which would be helpful to clarify its role in the treatment of RA.

scholarly journals Legionella pneumophila Replication in Macrophages Inhibited by Selective Immunomodulatory Effects on Cytokine Formation by Epigallocatechin Gallate, a Major Form of Tea Catechins

2001 ◽  
Vol 69 (6) ◽  
pp. 3947-3953 ◽  
Author(s):  
Kazuto Matsunaga ◽  
Thomas W. Klein ◽  
Herman Friedman ◽  
Yoshimasa Yamamoto
Keyword(s):  
Legionella Pneumophila ◽  
Biological Activities ◽  
Epigallocatechin Gallate ◽  
High Dose ◽  
Dependent Manner ◽  
Enhanced Production ◽  
Major Form ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Epigallocatechin gallate (EGCg) is a major form of tea catechin and has a variety of biological activities, including antitumor as well as antimicrobial activity against some pathogens. Although the biological activities of EGCg have been extensively studied, its immunological effects are not well known. In the present study, the ability of EGCg to modulate macrophage immune functions in an in vitro Legionella pneumophila infection model of macrophages was examined. The study showed that EGCg inhibited the growth of L. pneumophila in macrophages at a concentration as low as 0.5 μg/ml without any direct antibacterial effect on the organisms. The EGCg selectively upregulated the production of interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) and downregulated IL-10 production of macrophages induced by L. pneumophilainfection in a dose-dependent manner, but did not alter IL-6 production even at a high dose. The upregulation of the levels of macrophage gamma interferon (IFN-γ) mRNA by EGCg was also demonstrated. Treatment of macrophage cultures with anti-TNF-α and anti-IFN-γ monoclonal antibodies markedly abolished the anti-L. pneumophilaactivity of macrophages induced by the EGCg treatment. These results indicate that EGCg selectively alters the immune responses of macrophages to L. pneumophila and leads to an enhanced anti-L. pneumophila activity of macrophages mediated by enhanced production of both TNF-α and IFN-γ. However, the enhancement of in vitro anti-L. pneumophila activity by EGCg may not be directly mediated by IL-10 and IL-12 production modulation. Thus, the results of this study revealed the immunomodulatory effect of EGCg on macrophages, which have a critical role in infections.

scholarly journals Uncommon Bis-Amide Matrine-type Alkaloids From Sophora alopecuroides With Anti-inflammatory Effects

2021 ◽  
Vol 9 ◽  
Author(s):  
Ding Luo ◽  
Zhenchao Tu ◽  
Wenjing Yin ◽  
Chunlin Fan ◽  
Nenghua Chen ◽  
...  
Keyword(s):  
Dependent Manner ◽  
X Ray Diffraction ◽  
Sophora Alopecuroides ◽  
Tnf Α ◽  
Ic50 Values ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Dose Dependent ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Four new alkaloids (1–4) belonging to rare examples of bis-amide matrine-type were isolated from the seeds of sophora alopecuroides. Their structures including absolute configuration were determined by extensive spectroscopic analysis, electronic circular dichroism (ECD) interpretation, and X-ray diffraction crystallography. Chemically, bis-amide matrine-type alkaloids can provide new molecular template for structural modification. Compounds 3–4 displayed obvious anti-inflammatory effects based on the inhibition of two key pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in a dose-dependent manner, with IC50 values from 35.6 to 45.8 μm.

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