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 ◽  
...  

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.

2005 ◽  
Vol 230 (9) ◽  
pp. 645-651 ◽  
Author(s):  
James Rogers ◽  
Izabella Perkins ◽  
Alberto van Olphen ◽  
Nicholas Burdash ◽  
Thomas W. Klein ◽  
...  

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.


2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Narisara Paradee ◽  
Niramon Utama-ang ◽  
Chairat Uthaipibull ◽  
John B. Porter ◽  
Maciej W. Garbowski ◽  
...  

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).


2005 ◽  
Vol 2 (3) ◽  
pp. 149-153
Author(s):  
Lin Ya-Qiu ◽  
Li Rui-Wen ◽  
Sun Chao ◽  
Chen Guo-Zhu ◽  
Yang Yong-Qing ◽  
...  

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.


Dose-Response ◽  
2018 ◽  
Vol 16 (2) ◽  
pp. 155932581877497 ◽  
Author(s):  
Xiaoyu Lai ◽  
Jing Wei ◽  
Xinghong Ding

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.


2021 ◽  
Vol 9 ◽  
Author(s):  
Ding Luo ◽  
Zhenchao Tu ◽  
Wenjing Yin ◽  
Chunlin Fan ◽  
Nenghua Chen ◽  
...  

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.


2019 ◽  
Vol 48 (3) ◽  
pp. 030006051987346 ◽  
Author(s):  
Jun Zhang ◽  
Jing Yin ◽  
Daohong Zhao ◽  
Chaoran Wang ◽  
Yuhao Zhang ◽  
...  

Objective To study the therapeutic effect and mechanism of action of quercetin in a rat model of osteoarthritis (OA). Methods The OA rat model was established by intra-articular injection of papain. Changes in knee diameter, toe volume and histopathology were measured. Levels of interleukin (IL)-β and tumor necrosis factor (TNF)-α were assessed by ELISA. Relative expression of Toll-like receptor (TLR)-4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was evaluated by western blotting. Results Compared with rats treated with papain alone, changes in knee diameter, toe volume and Makin' s score were less apparent in OA rats treated with quercetin. Levels of serum IL-1β and TNF-α were also reduced in quercetin-treated OA rats. Expression of TLR-4 and NF-κB was significantly suppressed in a dose-dependent manner in quercetin-treated OA rats. Conclusion Quercetin exhibited a therapeutic effect in OA rats, which may be related to inhibition of IL-1β and TNF-α production via the TLR-4/NF-κB pathway.


2004 ◽  
Vol 11 (6) ◽  
pp. 1140-1147 ◽  
Author(s):  
Hidenori Matsuzaki ◽  
Hiroshi Kobayashi ◽  
Tatsuo Yagyu ◽  
Kiyoshi Wakahara ◽  
Toshiharu Kondo ◽  
...  

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.


2005 ◽  
Vol 33 (03) ◽  
pp. 415-424 ◽  
Author(s):  
Eunkyue Park ◽  
Susan Kum ◽  
Chuanhua Wang ◽  
Seung Yong Park ◽  
Bo Sook Kim ◽  
...  

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.


1999 ◽  
Vol 277 (5) ◽  
pp. L952-L959 ◽  
Author(s):  
Michael D. Wheeler ◽  
Ronald G. Thurman

Glycine blunts lipopolysaccharide (LPS)-induced increases in intracellular calcium concentration ([Ca2+]i) and tumor necrosis factor-α (TNF-α) production by Kupffer cells through a glycine-gated chloride channel. Alveolar macrophages, which have a similar origin as Kupffer cells, play a significant role in the pathogenesis of several lung diseases including asthma, endotoxemia, and acute inflammation due to inhaled bacterial particles and dusts. Therefore, studies were designed here to test the hypothesis that alveolar macrophages could be inactivated by glycine via a glycine-gated chloride channel. The ability of glycine to prevent endotoxin [lipopolysaccharide (LPS)]-induced increases in [Ca2+]iand subsequent production of superoxide and TNF-α in alveolar macrophages was examined. LPS caused a transient increase in intracellular calcium to nearly 200 nM, with EC50values slightly greater than 25 ng/ml. Glycine, in a dose-dependent manner, blunted the increase in [Ca2+]i, with an IC50less than 100 μM. Like the glycine-gated chloride channel in the central nervous system, the effects of glycine on [Ca2+]iwere both strychnine sensitive and chloride dependent. Glycine also caused a dose-dependent influx of radiolabeled chloride with EC50values near 10 μM, a phenomenon which was also inhibited by strychnine (1 μM). LPS-induced superoxide production was also blunted in a dose-dependent manner by glycine and was reduced ∼50% with 10 μM glycine. Moreover, TNF-α production was also inhibited by glycine and also required nearly 10 μM glycine for half-inhibition. These data provide strong pharmacological evidence that alveolar macrophages contain glycine-gated chloride channels and that their activation is protective against the LPS-induced increase in [Ca2+]iand subsequent production of toxic radicals and cytokines.


2019 ◽  
Vol 47 (7) ◽  
pp. 741-749 ◽  
Author(s):  
Yuko Arita ◽  
Hyeon Jeong Park ◽  
Aisling Cantillon ◽  
Darios Getahun ◽  
Ramkumar Menon ◽  
...  

Abstract Background Bisphenol-A (BPA) is a widespread pollutant whose effects on pregnant women are poorly understood. Therefore, we investigated the effects of BPA on basal and bacteria-stimulated production of proinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and IL-6], anti-inflammatory mediators [soluble glycoprotein 130 (sgp) 130, heme oxidase-1 (HO-1) and IL-10] and biomarkers for neurodevelopment [brain-derived neurotrophic factor (BDNF)], and oxidative stress [8-isoprostane (8-IsoP)] by the placenta. Methods Placental explant cultures were treated with BPA (0–10,000 nM) in the presence or absence of 107 colony-forming unit (CFU)/mL heat-killed Escherichia coli for 24 h. Biomarker concentrations in conditioned medium were quantified by the enzyme-linked immunosorbent assay (ELISA). Results Under basal conditions, IL-1β and IL-6 production was enhanced by BPA in a dose-dependent manner. Sgp130, a soluble receptor that reduces IL-6 bioactivity, was suppressed by BPA at 1000–10,000 nM. BPA also enhanced BDNF production at 1000 and 10,000 nM, and 8-IsoP expression at 10 and 100 nM. For bacteria-treated cultures, BPA increased IL-6 production at 100 nM and reduced sgp130 at 1000 nM but had no effect on IL-1β, TNF-α, BDNF, HO-1, 8-IsoP or IL-10 production. Conclusion BPA may increase placental inflammation by promoting IL-1β and IL-6 but inhibiting sgp130. It may also disrupt oxidative balance and neurodevelopment by increasing 8-IsoP and BDNF production.


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