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.

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.

Protein-free phospholipid emulsion treatment improved cardiopulmonary function and survival in porcine sepsis

2003 ◽  
Vol 284 (2) ◽  
pp. R550-R557 ◽  
Author(s):  
Roy D. Goldfarb ◽  
Thomas S. Parker ◽  
Daniel M. Levine ◽  
Dana Glock ◽  
Imran Akhter ◽  
...  
Keyword(s):  
Density Lipoprotein ◽  
Fibrin Clot ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Serum Lipoproteins ◽  
Treatment Groups ◽  
Tnf Α ◽  
Dose Dependent

Lipoprotein phospholipid (PL) plays a major role in neutralization of endotoxin. This study tested the hypothesis that prophylactic administration of a PL-enriched emulsion (PRE), which augments PL content of serum lipoproteins and neutralizes endotoxin in vitro, would preserve cardiovascular function and improve survival in porcine septic peritonitis. A control group was compared with low-, mid-, and high-dose treatment groups that received PRE by primed continuous infusion for 48 h. A fibrin clot containing live Escherichia coli 0111.B4 was implanted intraperitoneally 30 min after the priming dose. Survival increased in a dose-dependent manner and was correlated with serum PL. Infused PL was associated with high-density lipoprotein in the low-dose group and all serum lipoproteins at higher doses. Treatment significantly lowered serum endotoxin and tumor necrosis factor (TNF)-α, preserved cardiac output and ejection fraction, and attenuated increases in systemic and pulmonary vascular resistances. This study demonstrated that augmentation of lipoprotein PL via administration of PRE improved survival and offered a novel therapeutic approach to sepsis.

scholarly journals Epigallocatechin Gallate, a Potential Immunomodulatory Agent of Tea Components, Diminishes Cigarette Smoke Condensate-Induced Suppression of Anti-Legionella pneumophila Activity and Cytokine Responses of Alveolar Macrophages

2002 ◽  
Vol 9 (4) ◽  
pp. 864-871 ◽  
Author(s):  
Kazuto Matsunaga ◽  
Thomas W. Klein ◽  
Herman Friedman ◽  
Yoshimasa Yamamoto
Keyword(s):  
Antimicrobial Activity ◽  
Immune Responses ◽  
Cigarette Smoke ◽  
Alveolar Macrophages ◽  
Legionella Pneumophila ◽  
Epigallocatechin Gallate ◽  
Cigarette Smoke Condensate ◽  
Tnf Α ◽  
Ifn Γ ◽  
Bacterial Replication

ABSTRACT Even though cigarette smoking has been shown to suppress immune responses in the lungs, little is known about the effect of cigarette smoke components on respiratory infections. In the present study, the effects of cigarette smoke condensate (CSC) on bacterial replication in alveolar macrophages and the immune responses of macrophages to infection were examined. Furthermore, a possible immunotherapeutic effect of epigallocatechin gallate (EGCg), a major form of tea catechins, on the CSC-induced suppression of antimicrobial activity and immune responses of alveolar macrophages was also determined. The treatment of murine alveolar macrophage cell line (MH-S) cells with CSC significantly enhanced the replication of Legionella pneumophila in macrophages and selectively down-regulated the production of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) induced by bacterial infection. The treatment of macrophages with EGCg not only overcame the CSC-induced suppression of antimicrobial activity but also strengthened the resistance of macrophages to infection. EGCg also markedly up-regulated the CSC-suppressed IL-6 and TNF-α production by macrophages in response to infection. The results of exogenous TNF-α treatment and neutralization treatment with anti-TNF-α and anti-gamma-interferon (IFN-γ) antibodies and the determination of IFN-γ mRNA levels indicate that CSC-suppressed macrophages can be activated by EGCg to inhibit L. pneumophila growth by up-regulation of TNF-α and IFN-γ production. Thus, this study revealed that CSC selectively alters the immune responses of macrophages to L. pneumophila infection and leads to an enhancement of bacterial replication in macrophages. In addition, the tea catechin EGCg can diminish such suppressive effects of CSC on alveolar macrophages.

Role of Human NK Cells in Dentric-Cell Based Vaccine.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1550-1550
Author(s):  
Gerard M.J. Bos ◽  
Janine CHMJ Van Elssen ◽  
Joris Vanderlocht ◽  
Brigitte LMG Senden-Gijsbers ◽  
Wilfred LMG Germeraad
Keyword(s):  
Nk Cells ◽  
Human Study ◽  
Dependent Manner ◽  
Gm Csf ◽  
Tnf Α ◽  
Toll Like Receptor 2 ◽  
Ifn Γ ◽  
Th1 Polarization ◽  
Dc Maturation

Abstract Figure Figure Besides their prominent role in the destruction of altered self-cells, natural killer (NK) cells have been shown to potentiate T cell responses by interacting with dendritic cells (DC). In mouse models as well as in a recent human study it has been demonstrated that DC might activate NK cells. In the context of dendritic cell-based vaccines – i.e. optimising the optimal maturation cocktail - it remains to be determined if and how NK-DC interactions depend on differential DC maturation and what factors influence the NK activation.. By comparing differential DC differentiation (IL-4/GM-CSF and IL-13/GMCSF) and maturation cocktails (IFN-γ/FMKp and PGE2/TNF-α), we show that the ability of human DCs to attract NK cells is imprinted during DC maturation. Only FMKP/IFN-γ (stimulation Toll like receptor 2 and 4) maturated DCs have the capacity to actively recruit NK cells in vitro and our data indicate that CCR5 is the dominant chemokine receptor in this recruitment (Figure 1). Furthermore, in contrast to PGE2/TNF-α matured DC, FMKP/IFN-γ maturated DCs activate NK cells to produce IFN-γ in a IL-12/IL18 dependent manner, of which we show it contributes to strong TH1 polarization. In addition upon contact with these DCs NK cells upregulate their lymph node homing receptors, possibly inducing secondary migration to the lymph nodes. In conclusion, besides the identification of a superior DC maturation cocktail which contributes to NK-DC interactions, we identified a novel recruitment mechanism for peripheral human NK cells which may contribute to secondary, central DC-NK interactions and strong TH1 polarization.

scholarly journals Production of Matrix Metalloproteinases in Response to Mycobacterial Infection

2001 ◽  
Vol 69 (9) ◽  
pp. 5661-5670 ◽  
Author(s):  
Marianne Quiding-Järbrink ◽  
Debbie A. Smith ◽  
Gregory J. Bancroft
Keyword(s):  
Matrix Metalloproteinases ◽  
Severe Combined Immunodeficiency ◽  
Tissue Remodeling ◽  
Mycobacterial Infection ◽  
Dependent Manner ◽  
Mycobacterial Infections ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Matrix metalloproteinases (MMPs) constitute a large family of enzymes with specificity for the various proteins of the extracellular matrix which are implicated in tissue remodeling processes and chronic inflammatory conditions. To investigate the role of MMPs in immunity to mycobacterial infections, we incubated murine peritoneal macrophages with viable Mycobacterium bovis BCG or Mycobacterium tuberculosis H37Rv and assayed MMP activity in the supernatants by zymography. Resting macrophages secreted only small amounts of MMP-9 (gelatinase B), but secretion increased dramatically in a dose-dependent manner in response to either BCG or M. tuberculosis in vitro. Incubation with mycobacteria also induced increased MMP-2 (gelatinase A) activity. Neutralization of tumor necrosis alpha (TNF-α), and to a lesser extent interleukin 18 (IL-18), substantially reduced MMP production in response to mycobacteria. Exogenous addition of TNF-α or IL-18 induced macrophages to express MMPs, even in the absence of bacteria. The immunoregulatory cytokines gamma interferon (IFN-γ), IL-4, and IL-10 all suppressed BCG-induced MMP production, but through different mechanisms. IFN-γ treatment increased macrophage secretion of TNF-α but still reduced their MMP activity. Conversely, IL-4 and IL-10 seemed to act by reducing the amount of TNF-α available to the macrophages. Finally, infection of BALB/c or severe combined immunodeficiency (SCID) mice with either BCG or M. tuberculosis induced substantial increases in MMP-9 activity in infected tissues. In conclusion, we show that mycobacterial infection induces MMP-9 activity both in vitro and in vivo and that this is regulated by TNF-α, IL-18, and IFN-γ. These findings indicate a possible contribution of MMPs to tissue remodeling processes that occur in mycobacterial infections.

scholarly journals Leukotriene B4 Induces Nitric Oxide Synthesis in Trypanosoma cruzi-Infected Murine Macrophages and Mediates Resistance to Infection

2002 ◽  
Vol 70 (8) ◽  
pp. 4247-4253 ◽  
Author(s):  
A. Talvani ◽  
F. S. Machado ◽  
G. C. Santana ◽  
A. Klein ◽  
L. Barcelos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Trypanosoma Cruzi ◽  
Leukotriene B4 ◽  
No Production ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT The production of nitric oxide (NO) by gamma interferon (IFN-γ)-activated macrophages is a major effector mechanism during experimental Trypanosoma cruzi infection. In addition to IFN-γ, chemoattractant molecules, such as platelet-activating factor (PAF) and CC chemokines, may also activate macrophages to induce NO and mediate the killing of T. cruzi in an NO-dependent manner. Here we investigated the ability of leukotriene B4 (LTB4) to induce the production of NO by macrophages infected with T. cruzi in vitro and whether NO mediated LTB4-induced parasite killing. The activation of T. cruzi-infected but not naive murine peritoneal macrophages with LTB4 induced the time- and concentration-dependent production of NO. In addition, low concentrations of LTB4 acted in synergy with IFN-γ to induce NO production. The NO produced mediated LTB4-induced microbicidal activity in macrophages, as demonstrated by the inhibitory effects of an inducible NO synthase inhibitor. LTB4-induced NO production and parasite killing were LTB4 receptor dependent and were partially blocked by a PAF receptor antagonist. LTB4 also induced significant tumor necrosis factor alpha (TNF-α) production, and blockade of TNF-α suppressed LTB4-induced NO release and parasite killing. A blockade of LTB4 or PAF receptors partially inhibited IFN-γ-induced NO and TNF-α production but not parasite killing. Finally, daily treatment of infected mice with CP-105,696 was accompanied by a significantly higher level of blood parasitemia, but not lethality, than that seen in vehicle-treated animals. In conclusion, our results suggest a role for LTB4 during experimental T. cruzi infection. Chemoattractant molecules such as LTB4 not only may play a major role in leukocyte migration into sites of inflammation in vivo but also, in the event of an infection, may play a relevant role in the activation of recruited leukocytes to kill the invading microorganism in an NO-dependent manner.

scholarly journals Immunophenotype and Immune-Modulatory Activities of Human Fetal Cartilage-Derived Progenitor Cells

2019 ◽  
Vol 28 (7) ◽  
pp. 932-942 ◽  
Author(s):  
Su Jeong Lee ◽  
Jiyoung Kim ◽  
Woo Hee Choi ◽  
So Ra Park ◽  
Byung Hyune Choi ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Hla Class I ◽  
Peripheral Blood Lymphocytes ◽  
Dependent Manner ◽  
Con A ◽  
Hla Class I Molecules ◽  
Tnf Α ◽  
Adult Mesenchymal Stem Cells ◽  
Ifn Γ

We have previously reported human fetal cartilage progenitor cells (hFCPCs) as a novel source of therapeutic cells showing high proliferation and stem cell properties superior to those of adult mesenchymal stem cells (MSCs). In this study, we investigated the immunophenotype and immune-modulatory activities of hFCPCs. With institutional review board approval, hFCPCs were isolated from fetuses at 11–13 weeks of gestation. hFCPCs showed strong expression of HLA class I molecules but low or no expression of HLA class II and co-stimulatory molecules, which was not changed significantly after 4 days of IFN-γ treatment. In a mixed lymphocyte reaction (MLR), hFCPCs showed no allogeneic immune response to peripheral blood lymphocytes (PBLs) and suppressed concanavalin A (Con A)-mediated proliferation of PBLs in a dose-dependent manner. In addition, hFCPCs inhibited Con A-induced secretion of pro-inflammatory cytokines TNF-α and IFN-γ from PBLs but showed no significant decrease of secretion of IL-10, anti-inflammatory cytokine. Co-culture of hFCPCs with stimulated PBLs for 4 days resulted in a significant increase in CD4+CD25+FoxP3+ T regulatory cells (Tregs). hFCPCs expressed LIF, TGF-β1, TSG-6, and sHLA-G5 but did not express IDO and HGF. Stimulation of hFCPCs with TNF-α for 12 h showed slight induction in the expression of LIF, TSG-6, IDO, and HGF, whereas stimulation with IFN-γ did not affect expression of any of these factors. These results suggest that hFCPCs have low allogeneic immunogenicity and immune-modulatory activity in vitro, comparable to those of MSCs. However, compared with MSCs, hFCPCs were less responsive to TNF-α and IFN-γ, and the mechanisms underlying responses to these two cell types appeared distinct.

scholarly journals In VitroAnalyses of the Effects of Heparin and Parabens on Candida albicans Biofilms and Planktonic Cells

2011 ◽  
Vol 56 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Marisa H. Miceli ◽  
Stella M. Bernardo ◽  
T. S. Neil Ku ◽  
Carla Walraven ◽  
Samuel A. Lee
Keyword(s):  
Candida Albicans ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
High Dose ◽  
Dependent Manner ◽  
Planktonic Cells ◽  
Content Type ◽  
Heparin Sodium ◽  
The Individual

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.

scholarly journals Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Fabiana Albani Zambuzi ◽  
Priscilla Mariane Cardoso-Silva ◽  
Ricardo Cardoso Castro ◽  
Caroline Fontanari ◽  
Flavio da Silva Emery ◽  
...  
Keyword(s):  
Immune Response ◽  
Hematological Malignancies ◽  
M2 Macrophage ◽  
M2 Polarization ◽  
Tnf Α ◽  
Monocytes And Macrophages ◽  
Ifn Γ ◽  
And Function ◽  
The Impact

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.

scholarly journals Bioactivity-Guided Extract Optimization of Osmanthus fragrans var. aurantiacus Leaves and Anti-Inflammatory Activities of Phillyrin

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1545
Author(s):  
Hwa-Young Song ◽  
Da-Eun Jeong ◽  
Mina Lee
Keyword(s):  
Biological Activities ◽  
Radical Scavenging ◽  
No Production ◽  
Dependent Manner ◽  
Optimal Method ◽  
Concentration Dependent Manner ◽  
Osmanthus Fragrans ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Extracellular Regulated Kinase

The aim of this study was to identify the optimal extraction conditions for leaves of Osmanthus fragrans var. aurantiacus. Inhibitory effects of various extracts on NO production were compared. Antioxidant evaluations for total phenol and flavonoid contents were carried out using various extracts of O. fragrans var. aurantiacus leaves obtained under optimal extraction conditions that showed the greatest effect on NO production. The optimal method for extracting O. fragrans var. aurantiacus leaves resulted in an extract named OP OFLE. OP OFLE showed DPPH and ABTS radical scavenging activities in a concentration-dependent manner. Phillyrin (PH) was isolated as a major compound from OP OFLE by HPLC/DAD analysis. OP OFLE and PH reduced inducible nitric oxide (iNOS) and cyclooxygenase (COX)-2 protein expression and downregulated proinflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in LPS-stimulated RAW 264.7 and HT-29 cells. To determine the signal pathway involved in the inhibition of NO production, a Western blot analysis was performed. Results showed that OP OFLE decreased phosphorylation of extracellular regulated kinase (pERK) 1/2 and the expression of nuclear factor-kappa B (NF-κB). Our results suggest that extracts of O. fragrans var. aurantiacus leaves and its major components have biological activities such as antioxidative and anti-inflammatory properties.

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