scholarly journals The Staphyloccous aureus Eap Protein Activates Expression of Proinflammatory Cytokines

2008 ◽  
Vol 76 (5) ◽  
pp. 2164-2168 ◽  
Author(s):  
Thomas J. Scriba ◽  
Sophie Sierro ◽  
Eric L. Brown ◽  
Rodney E. Phillips ◽  
Andrew K. Sewell ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Monocytes And Macrophages

ABSTRACT The extracellular adhesion protein (Eap) secreted by the major human pathogen Staphylococcus aureus is known to have several effects on human immunity. We have recently added to knowledge of these roles by demonstrating that Eap enhances interactions between major histocompatibility complex molecules and human leukocytes. Several studies have indicated that Eap can induce cytokine production by human peripheral blood mononuclear cells (PBMCs). To date, there has been no rigorous attempt to identify the breadth of cytokines produced by Eap stimulation or to identify the cell subsets that respond. Here, we demonstrate that Eap induces the secretion of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) by CD14+ leukocytes (monocytes and macrophages) within direct ex vivo PBMC populations (note that granulocytes are also CD14+ but are largely depleted from PBMC preparations). Anti-intercellular adhesion molecule 1 (CD54) antibodies inhibited this induction and implicated a role for this known Eap binding protein in cellular activation. IL-6 and TNF-α secretion by murine cells exposed to Eap was also observed. The activation of CD14+ cells by Eap suggests that it could play a significant role in both septic shock and fever, two of the major pathological features of S. aureus infections.

scholarly journals Differential In Vitro Cytokine Induction by the Species of Cryptococcus gattii Complex

2018 ◽  
Vol 86 (4) ◽  
Author(s):  
Patricia F. Herkert ◽  
Jessica C. dos Santos ◽  
Ferry Hagen ◽  
Fatima Ribeiro-Dias ◽  
Flávio Queiroz-Telles ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Sensu Stricto ◽  
Cryptococcus Gattii ◽  
The Other ◽  
Human Pbmcs ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α

ABSTRACT Cryptococcal species vary in capsule and cell size, thermotolerance, geographic distribution, and affected populations. Cryptococcus gattii sensu stricto and C. deuterogattii affect mainly immunocompetent hosts; however, C. bacillisporus , C. decagattii , and C. tetragattii cause infections mainly in immunocompromised hosts. This study aimed to compare the capacities of different species of the C. gattii species complex to induce cytokines and antimicrobial molecules in human peripheral blood mononuclear cells (PBMCs). Cryptococcus bacillisporus and C. deuterogattii induced the lowest levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 among the five species of the C. gattii complex. Cryptococcus deuterogattii induced higher levels of IL-22 than those induced by C. tetragattii and the environmental species C. flavescens . In addition, C. bacillisporus and C. gattii sensu stricto proliferated inside human monocyte-derived macrophages after 24 h of infection. All Cryptococcus species were able to generate reactive oxygen species (ROS) in human PBMCs, with C. bacillisporus and C. deuterogattii being more efficient than the other species. In conclusion, C. bacillisporus and C. deuterogattii induce lower levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 and higher ROS levels than those induced by the other species. Species of the Cryptococcus gattii complex have different abilities to induce cytokine and ROS production by human PBMCs.

scholarly journals Immunomodulating Properties of the Antibiotic Novobiocin in Human Monocytes

1998 ◽  
Vol 42 (8) ◽  
pp. 1911-1916 ◽  
Author(s):  
Anja Lührmann ◽  
Jürgen Thölke ◽  
Ingrid Behn ◽  
Jens Schumann ◽  
Gisa Tiegs ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Interleukin 1 ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Adp Ribosylation ◽  
Surface Molecules ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT We show that the coumeromycin antibiotic novobiocin, a potent inhibitor of ADP ribosylation, prevents lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, and IL-10 secretion in human peripheral blood mononuclear cells. It shares these cytokine-suppressing properties with other inhibitors of ADP ribosylation. We found that novobiocin prevents TNF-α production by inhibiting translation of the TNF-α mRNA. Elevated TNF-α levels in mice treated withd-galactosamine (GalN)-LPS or GalN-TNF were not reduced by novobiocin; however, the drug exhibited hepatoprotective properties. Novobiocin causes downregulation of the surface molecules on monocytes, among which CD14 was the most affected. The diminished expression of surface molecules was not observed on T and B lymphocytes. Similar to other inhibitors of ADP ribosylation, novobiocin prevents LPS-induced phosphate labelling of γ-actins.

scholarly journals Effect of Moxifloxacin on Production of Proinflammatory Cytokines from Human Peripheral Blood Mononuclear Cells

2003 ◽  
Vol 47 (12) ◽  
pp. 3704-3707 ◽  
Author(s):  
Jung-Hyun Choi ◽  
Min-Jin Song ◽  
Seung-Han Kim ◽  
Su-Mi Choi ◽  
Dong-Gun Lee ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Blood Mononuclear Cells

ABSTRACT The effects of moxifloxacin, a new methoxyfluoroquinolone, on the production of proinflammatory cytokines from human peripheral blood mononuclear cells (PBMCs) were evaluated. Moxifloxacin inhibited the production of tumor necrosis factor alpha (TNF-α) and/or interleukin-6 (IL-6) by PBMCs stimulated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), and heat-killed bacteria in a concentration-dependent manner without cytotoxic effects. The addition of moxifloxacin reduced the population of cells positive for CD-14 and TNF-α and for CD-14 and IL-6 among the LPS- or LTA-stimulated PBMCs. By Western blot analysis, moxifloxacin pretreatment reduced the degradation of IκBα in LPS-stimulated PBMCs. In conclusion, moxifloxacin could interfere with NF-κB activation by inhibiting the degradation of IκBα and reduce the levels of production of proinflammatory cytokines.

scholarly journals Platelet Microparticles Enriched in miR-223 Reduce ICAM-1-Dependent Vascular Inflammation in Septic Conditions

2021 ◽  
Vol 12 ◽  
Author(s):  
Bernadett Szilágyi ◽  
Zsolt Fejes ◽  
Ágnes Rusznyák ◽  
Ferenc Fenyvesi ◽  
Marianna Pócsi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mononuclear Cells ◽  
Vascular Inflammation ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Human Coronary Artery ◽  
Peripheral Blood Mononuclear ◽  
Gene Target ◽  
Mirna Level ◽  
Tnf Α

In the process of sepsis, activated platelets shed microvesicles containing microRNAs (miRNAs), which can be internalized by distinct recipient cells in circulation, consequently eliciting a potent capability to regulate their cellular functions in different diseases. In the present study, activated human platelets transferring miR-223 into endothelial cells via platelet-derived microparticles (PMPs) was investigated in vitro during septic conditions with a proposed mechanism involving in downregulation of the enhanced expression of intercellular adhesion molecule-1 (ICAM-1). The uptake of PMPs encasing miR-223 and the adhesion of peripheral blood mononuclear cells (PBMCs) on human coronary artery endothelial cells (HCAECs) were observed by immunofluorescence microscopy upon co-culture with PMPs isolated from sepsis or control plasma. The expression of miR-223-3p and its gene target ICAM1 in HCAECs were quantified by RT-qPCR and ELISA after the cells were incubated with septic or control PMPs, whose levels were induced with thrombin-receptor activating peptide (TRAP). Leukocyte-depleted platelets (LDPs) from septic patients showed a decreased miR-223 level, while septic plasma and PMPs revealed an elevated miRNA level compared to control samples. Similarly, TRAP-activated LDPs demonstrated a reduced intracellular miR-223 expression, while increased levels in the supernatant and PMP isolates were observed vs. untreated samples. Furthermore, TNF-α alone resulted in decreased miR-223 and elevated ICAM1 levels in HCAECs, while PMPs raised the miRNA level that was associated with downregulated ICAM1 expression at both mRNA and protein levels under TNF-α treatment. Importantly, miR-223 was turned out not to be newly synthesized as shown in unchanged pre-miR-223 level, and mature miR-223 expression was also elevated in the presence of PMPs in HCAECs after transfection with Dicer1 siRNA. In addition, septic PMPs containing miR-223 decreased ICAM1 with a reduction of PBMC binding to HCAECs. In conclusion, septic platelets released PMPs carrying functional miR-223 lower ICAM1 expression in endothelial cells, which may be a protective role against excessive sepsis-induced vascular inflammation.

scholarly journals Salmonella typhi Flagella Are Potent Inducers of Proinflammatory Cytokine Secretion by Human Monocytes

1999 ◽  
Vol 67 (7) ◽  
pp. 3619-3624 ◽  
Author(s):  
Timothy L. Wyant ◽  
Michael K. Tanner ◽  
Marcelo B. Sztein
Keyword(s):  
Mononuclear Cells ◽  
Vaccine Development ◽  
De Novo ◽  
Human Peripheral Blood ◽  
Polymyxin B ◽  
Salmonella Typhi ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Monocyte Subpopulations

ABSTRACT The cytokine production patterns of human peripheral blood mononuclear cells (PBMC) in response to Salmonella typhiflagella (STF) were examined in culture supernatants of PBMC stimulated with STF. Consistent with previous findings in volunteers vaccinated with aroC aroD deletion mutants of S. typhi, PBMC from volunteers immunized with the licensed live Ty21a S. typhi vaccine secreted gamma interferon following exposure to STF. Stimulation with STF induced rapid de novo synthesis of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β), followed by IL-6 and IL-10. Trypsin treatment of STF abrogated their effects, while polymyxin B had no effect. Intracellular cytokine measurements of STF-stimulated PBMC revealed the existence of monocyte subpopulations that produce only TNF-α, IL-1β or both cytokines. Moreover, STF markedly decreased the percentage of CD14+cells. These data demonstrate that STF are powerful monocyte activators which may have important implications for vaccine development and for understanding the pathogenesis of S. typhi infection.

scholarly journals Pentoxifylline Inhibits Superantigen-Induced Toxic Shock and Cytokine Release

1999 ◽  
Vol 6 (4) ◽  
pp. 594-598 ◽  
Author(s):  
Teresa Krakauer ◽  
Bradley G. Stiles
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Toxic Shock ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ ◽  
Toxic Shock Syndrome Toxin

ABSTRACT Tumor necrosis factor alpha (TNF-α) is a critical cytokine that mediates the toxic effects of bacterial superantigens like staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin 1 (TSST-1). Pentoxifylline, an anti-inflammatory agent that inhibits endotoxemia and lipopolysaccharide (LPS)-induced release of TNF-α, was tested for its ability to inhibit SEB- and TSST-1-induced activation of human peripheral blood mononuclear cells (PBMCs) in vitro and toxin-mediated shock in mice. Stimulation of PBMCs by SEB or TSST-1 was effectively blocked by pentoxifylline (10 mM), as evidenced by the inhibition of TNF-α, interleukin 1β (IL-1β), gamma interferon (IFN-γ), and T-cell proliferation. The levels of TNF-α, IL-1α, and IFN-γ in serum after an SEB or TSST-1 injection were significantly lower in mice given pentoxifylline (5.5 mg/animal) versus control mice. Additionally, pentoxifylline diminished the lethal effects and temperature fluctuations elicited by SEB and TSST-1. Thus, in addition to treating endotoxemias, the cumulative in vitro and in vivo data suggest that pentoxifylline may also be useful in abrogating the ill effects of staphylococcal enterotoxins and TSST-1.

scholarly journals Integrated cytokine and metabolite analysis reveals immunometabolic reprogramming in COVID-19 patients with therapeutic implications

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nan Xiao ◽  
Meng Nie ◽  
Huanhuan Pang ◽  
Bohong Wang ◽  
Jieli Hu ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Rhesus Macaques ◽  
Fatal Outcome ◽  
Organ Injury ◽  
Cytokine Release ◽  
Serum Samples ◽  
Peripheral Blood Mononuclear

AbstractCytokine release syndrome (CRS) is a major cause of the multi-organ injury and fatal outcome induced by SARS-CoV-2 infection in severe COVID-19 patients. Metabolism can modulate the immune responses against infectious diseases, yet our understanding remains limited on how host metabolism correlates with inflammatory responses and affects cytokine release in COVID-19 patients. Here we perform both metabolomics and cytokine/chemokine profiling on serum samples from healthy controls, mild and severe COVID-19 patients, and delineate their global metabolic and immune response landscape. Correlation analyses show tight associations between metabolites and proinflammatory cytokines/chemokines, such as IL-6, M-CSF, IL-1α, IL-1β, and imply a potential regulatory crosstalk between arginine, tryptophan, purine metabolism and hyperinflammation. Importantly, we also demonstrate that targeting metabolism markedly modulates the proinflammatory cytokines release by peripheral blood mononuclear cells isolated from SARS-CoV-2-infected rhesus macaques ex vivo, hinting that exploiting metabolic alterations may be a potential strategy for treating fatal CRS in COVID-19.

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