scholarly journals Differential Roles of Interleukin-18 (IL-18) and IL-12 for Induction of Gamma Interferon by Staphylococcal Cell Wall Components and Superantigens

2001 ◽  
Vol 69 (8) ◽  
pp. 5025-5030 ◽  
Author(s):  
Rogier J. L. Stuyt ◽  
Mihai G. Netea ◽  
Soo-Hyun Kim ◽  
Daniela Novick ◽  
Menachem Rubinstein ◽  
...  
Keyword(s):  
Binding Protein ◽  
Gamma Interferon ◽  
Host Cells ◽  
Interleukin 18 ◽  
Toxic Shock ◽  
Ifn Γ ◽  
Toxic Shock Syndrome Toxin ◽  
Staphylococcus Enterotoxin B ◽  
Wall Components ◽  
Necrosis Factor

ABSTRACT The roles of endogenous cytokines induced by either intact staphylococcal microorganisms or staphylococcal exotoxins were examined using human whole-blood cultures. To accomplish this, interleukin-18 binding protein (IL-18BP) and tumor necrosis factor binding protein (TNFbp) were used to neutralize IL-18 and TNF, respectively, whereas an anti-IL-12 monoclonal antibody was used to neutralize IL-12 and the IL-1 receptor antagonist (IL-1Ra) was used to block IL-1 receptors. Heat-killed Staphylococcus epidermidis andStaphylococcus aureus, as well as the staphylococcal superantigens toxic shock syndrome toxin-1 (TSST-1) and staphylococcus enterotoxin B (SEB) induced gamma interferon (IFN-γ) production.Staphylococcus spp.-induced production of IFN-γ required the presence of endogenous IL-18, IL-12, and TNF. In contrast, TSST-1-induced IFN-γ was not significantly reduced in the presence of IL-18BP, anti-IL-12 antibodies, IL-1Ra, or anti-TNFbp. SEB-induced IFN-γ was significantly inhibited only by anti-IL-12 antibodies, indicating that endogenous IL-18, IL-1, and TNF are not required for SEB-induced IFN-γ. In conclusion, the mechanisms of IFN-γ stimulation by intact staphylococcal microorganisms and by exotoxins differ, and this is likely due to the different receptors which are triggered on the cell membranes. In contrast to its role in the interactions between staphylococci and host cells, IL-18 does not appear to play a major role in superantigen-induced IFN-γ.

scholarly journals Role of T Cells and Gamma Interferon during Induction of Hypersensitivity to Lipopolysaccharide by Toxic Shock Syndrome Toxin 1 in Mice

2001 ◽  
Vol 69 (3) ◽  
pp. 1256-1264 ◽  
Author(s):  
Martin M. Dinges ◽  
Patrick M. Schlievert
Keyword(s):  
T Cells ◽  
Toxic Shock Syndrome ◽  
Gamma Interferon ◽  
Scid Mice ◽  
Enhancement Effect ◽  
Toxic Shock ◽  
Tnf Α ◽  
Ifn Γ ◽  
Toxic Shock Syndrome Toxin

ABSTRACT The superantigenic function of toxic shock syndrome toxin 1 (TSST-1) is generally regarded as an important determinant of its lethal effects in humans or experimental animals. This study examined the role of superantigenicity in a BALB/c mouse model of lethal TSST-1-induced hypersensitivity to lipopolysaccharide (LPS). In this model, TSST-1 greatly potentiated both LPS-induced lethality, as well as LPS-induced serum tumor necrosis factor alpha (TNF-α) activity. Although BALB/c-SCID mice were resistant to these LPS enhancement effects of TSST-1, BALB/c-SCID mice reconstituted with T cells were completely susceptible to the enhancement effect of TSST-1 on LPS-induced serum TNF-α. Mice pretreated with cyclosporine (Cs) or neutralizing antibodies against gamma interferon (IFN-γ) did not develop lethal LPS hypersensitivity when injected with TSST-1, and these agents reduced the enhancement effect of TSST-1 on LPS-induced serum TNF-α by 99 and 85%, respectively. Cs pretreatment also completely inhibited the known capacity of TSST-1 to amplify LPS-induced levels of IFN-γ in serum. In contrast, mice given Cs after a priming injection of TSST-1, but before LPS, still exhibited lethal hypersensitivity to LPS. Cs given after TSST-1 also did not inhibit enhancement of LPS-induced serum TNF-α by TSST-1 but inhibited the enhancement effect of TSST-1 on LPS-induced serum IFN-γ by 50%. These experiments support the theory that TSST-1-induced hypersensitivity to LPS is mediated primarily by IFN-γ derived from superantigen-activated T cells.

scholarly journals Vaccinia Virus Interleukin-18-Binding Protein Promotes Virulence by Reducing Gamma Interferon Production and Natural Killer and T-Cell Activity

2003 ◽  
Vol 77 (18) ◽  
pp. 9960-9968 ◽  
Author(s):  
Patrick C. Reading ◽  
Geoffrey L. Smith
Keyword(s):  
T Cell ◽  
Vaccinia Virus ◽  
Cytotoxic Activity ◽  
Natural Killer ◽  
T Cell Activation ◽  
Binding Protein ◽  
Gamma Interferon ◽  
Interleukin 18 ◽  
Ifn Γ

ABSTRACT Interleukin-18 (IL-18) is a proinflammatory cytokine that promotes natural killer (NK) and T-cell activation. Several poxviruses, including vaccinia virus (VV), encode a soluble IL-18-binding protein (IL-18bp). The role of the VV IL-18bp (gene C12L) in vivo was studied with wild-type (vC12L), deletion mutant (vΔC12L), and revertant (vC12L-rev) viruses in a murine intranasal model of infection. The data show that vΔC12L was markedly attenuated, characterized by a mild weight loss and reduced virus titers in lungs, brain, and spleen. Three days after infection, NK cytotoxic activity was augmented in the lung, spleen, and mediastinal lymph nodes (MLNs) of vΔC12L-infected mice compared to controls. Seven days after infection, vΔC12L-infected mice displayed heightened VV-specific cytotoxic T-lymphocyte (CTL) responses in the lungs, spleen, and MLNs. Gamma interferon (IFN-γ) levels were also dramatically elevated in lavage fluids and cells from lungs of mice infected with vΔC12L. Finally, we demonstrate that IL-18 is produced in vitro and in vivo after VV infection. Taken together, these data demonstrate a role for the vIL-18bp in counteracting IL-18 in both the innate and the specific immune response to VV infection and indicate that the ability of IL-18 to promote vigorous T-cell responses (cytotoxic activity and IFN-γ production) is a critical factor in the accelerated clearance of the vΔC12L mutant.

scholarly journals Gamma Interferon and Lipopolysaccharide Interact at the Level of Transcription To Induce Tumor Necrosis Factor Alpha Expression

2001 ◽  
Vol 69 (5) ◽  
pp. 2847-2852 ◽  
Author(s):  
Julia Y. Lee ◽  
Kathleen E. Sullivan
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Gamma Interferon ◽  
Necrosis Factor Alpha ◽  
Rnase Protection ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Lipopolysaccharide (LPS) is a very potent inducer of tumor necrosis factor alpha (TNF-α) expression from monocytes and macrophages. Another inflammatory cytokine, gamma interferon (IFN-γ), can potentiate the effects of LPS, but the mechanism is not thoroughly understood. Previous reports emphasized the ability of IFN-γ to upregulate CD14 expression (the receptor for LPS), and nearly all studies have utilized sequential stimulation with IFN-γ followed by LPS to exploit this phenomenon. This study demonstrates that IFN-γ can upregulate the effect of LPS at the level of transcription. Human monoblastic Mono-Mac-6 cells produced up to threefold-greater levels of TNF-α when simultaneously stimulated with LPS and IFN-γ compared to treatment with LPS alone. RNase protection studies showed a similar increase in RNA beginning as early as within 30 min. The synthesis of TNF-α mRNA in IFN-γ- and LPS-treated Mono-Mac-6 cells was also temporally prolonged even though the message turnover rate was identical to that seen in LPS stimulated cells. The modulatory effect of IFN-γ may be mediated by Jak2.

scholarly journals Eugenol Reduces the Expression of Virulence-Related Exoproteins in Staphylococcus aureus

2010 ◽  
Vol 76 (17) ◽  
pp. 5846-5851 ◽  
Author(s):  
Jiazhang Qiu ◽  
Haihua Feng ◽  
Jing Lu ◽  
Hua Xiang ◽  
Dacheng Wang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Transcriptional Analysis ◽  
Pcr Analysis ◽  
Transcriptional Level ◽  
Toxic Shock ◽  
Release Assay ◽  
Subinhibitory Concentrations ◽  
Toxic Shock Syndrome Toxin ◽  
Culture Supernatants ◽  
Necrosis Factor

ABSTRACT Eugenol, an essential oil component in plants, has been demonstrated to possess activity against both Gram-positive and Gram-negative bacteria. This study examined the influence that subinhibitory concentrations of eugenol may have on the expression of the major exotoxins produced by Staphylococcus aureus. The results from a tumor necrosis factor (TNF) release assay and a hemolysin assay indicated that S. aureus cultured with graded subinhibitory concentrations of eugenol (16 to 128 μg/ml) dose dependently decreased the TNF-inducing and hemolytic activities of culture supernatants. Western blot analysis showed that eugenol significantly reduced the production of staphylococcal enterotoxin A (SEA), SEB, and toxic shock syndrome toxin 1 (the key exotoxins to induce TNF release), as well as the expression of α-hemolysin (the major hemolysin to cause hemolysis). In addition, this suppression was also evaluated at the transcriptional level via real-time reverse transcription (RT)-PCR analysis. The transcriptional analysis indicated that 128 μg/ml of eugenol remarkably repressed the transcription of the S. aureus sea, seb, tst, and hla genes. According to these results, eugenol has the potential to be rationally applied on food products as a novel food antimicrobial agent both to inhibit the growth of bacteria and to suppress the production of exotoxins by S. aureus.

Circulating concentrations of interleukin-18, interleukin-18 binding protein, and gamma interferon in patients with alcoholic hepatitis

2004 ◽  
Vol 24 (6) ◽  
pp. 582-587 ◽  
Author(s):  
Laurent Spahr ◽  
Irene Garcia ◽  
Solange Bresson-Hadni ◽  
Laura Rubbia-Brandt ◽  
Reto Guler ◽  
...  
Keyword(s):  
Alcoholic Hepatitis ◽  
Binding Protein ◽  
Gamma Interferon ◽  
Interleukin 18

scholarly journals Comparison of Gamma Interferon-Mediated Antichlamydial Defense Mechanisms in Human and Mouse Cells

2006 ◽  
Vol 74 (1) ◽  
pp. 225-238 ◽  
Author(s):  
Christine Roshick ◽  
Heidi Wood ◽  
Harlan D. Caldwell ◽  
Grant McClarty
Keyword(s):  
Nitric Oxide ◽  
Cell Lines ◽  
Human Cell ◽  
Mouse Cell ◽  
Gamma Interferon ◽  
Host Cells ◽  
Human Cell Lines ◽  
Mouse Cells ◽  
Ifn Γ ◽  
Human And Mouse

ABSTRACT Gamma interferon (IFN-γ)-induced effector mechanisms have potent antichlamydial activities that are critical to host defense. The most prominent and well-studied effectors are indoleamine dioxygenase (IDO) and nitric oxide (NO) synthase. The relative contributions of these mechanisms as inhibitors of chlamydial in vitro growth have been extensively studied using different host cells, induction mechanisms, and chlamydial strains with conflicting results. Here, we have undertaken a comparative analysis of cytokine- and lipopolysaccharide (LPS)-induced IDO and NO using an extensive assortment of human and murine host cells infected with human and murine chlamydial strains. Following cytokine (IFN-γ or tumor necrosis factor alpha) and/or LPS treatment, the majority of human cell lines induced IDO but failed to produce NO. Conversely, the majority of mouse cell lines studied produced NO, not IDO. Induction of IDO in human cell lines inhibited growth of L2 and mouse pneumonitis agent, now referred to as Chlamydia muridarum MoPn equally in all but two lines, and inhibition was completely reversible by the addition of tryptophan. IFN-γ treatment of mouse cell lines resulted in substantially greater reduction of L2 than MoPn growth. However, despite elevated NO production by murine cells, blockage of NO synthesis with the l-arginine analogue N-monomethyl-l-arginine only partially rescued chlamydial growth, suggesting the presence of another IFN-γ-inducible antichlamydial mechanism unique to murine cells. Moreover, NO generated from the chemical nitric oxide donor sodium nitroprusside showed little direct effect on chlamydial infectivity or growth, indicating a natural resistance to NO. Finally, IFN-γ-inducible IDO expression in human HeLa cells was inhibited following exogenous NO treatment, resulting in a permissive environment for chlamydial growth. In summary, cytokine- and LPS-inducible effectors produced by human and mouse cells differ and, importantly, these host-specific effector responses result in chlamydial strain-specific antimicrobial activities.

scholarly journals The Gamma Interferon (IFN-γ)-Inducible GTP-Binding Protein IGTP Is Necessary for Toxoplasma Vacuolar Disruption and Induces Parasite Egression in IFN-γ-Stimulated Astrocytes

2008 ◽  
Vol 76 (11) ◽  
pp. 4883-4894 ◽  
Author(s):  
T. Melzer ◽  
A. Duffy ◽  
L. M. Weiss ◽  
S. K. Halonen
Keyword(s):  
Host Cell ◽  
Fluorescent Protein ◽  
Binding Protein ◽  
Parasitophorous Vacuole ◽  
Central Nervous System Infection ◽  
Gamma Interferon ◽  
Gtp Binding Protein ◽  
Gtp Binding ◽  
Ifn Γ ◽  
Green Fluorescent

ABSTRACT Toxoplasma gondii is a common central nervous system infection in individuals with immunocompromised immune systems, such as AIDS patients. Gamma interferon (IFN-γ) is the main cytokine mediating protection against T. gondii. Our previous studies found that IFN-γ significantly inhibits T. gondii in astrocytes via an IFN-γ-inducible GTP-binding protein (IGTP)-dependent mechanism. The IGTP-dependent-, IFN-γ-stimulated inhibition is not understood, but recent studies found that IGTP induces disruption of the parasitophorous vacuole (PV) in macrophages. In the current study, we have further investigated the mechanism of IFN-γ inhibition and the role of IGTP in the vacuolar disruption in murine astrocytes. Vacuolar disruption was found to be dependent upon IGTP, as PV disruption was not observed in IGTP-deficient (IGTP−/−) astrocytes and PV disruption could be induced in IGTP−/− astrocytes transfected with IGTP. Live-cell imaging studies using green fluorescent protein-IGTP found that IGTP is delivered to the PV via the host cell endoplasmic reticulum (ER) early after invasion and that IGTP condenses into vesicle-like structures on the vacuole just prior to PV disruption, suggesting that IGTP is involved in PV disruption. Intravacuolar movement of the parasite occurred just prior to PV disruption. In some instances, IFN-γ induced parasite egression. Electron microscopy and immunofluorescence studies indicate that the host cell ER fuses with the PV prior to vacuolar disruption. On the basis of these results, we postulate a mechanism by which ER/PV fusion is a crucial event in PV disruption. Fusion of the ER with the PV, releasing calcium into the vacuole, may also be the mechanism by which intravacuolar parasite movement and IFN-γ-induced parasite egression occur.

scholarly journals Porphyromonas gingivalis, Gamma Interferon, and a Proapoptotic Fibronectin Matrix Form a Synergistic Trio That Induces c-Jun N-Terminal Kinase 1-Mediated Nitric Oxide Generation and Cell Death

2008 ◽  
Vol 76 (12) ◽  
pp. 5514-5523 ◽  
Author(s):  
Abhijit Ghosh ◽  
Ji Young Park ◽  
Christopher Fenno ◽  
Yvonne L. Kapila
Keyword(s):  
Nitric Oxide ◽  
Porphyromonas Gingivalis ◽  
Gamma Interferon ◽  
Host Cells ◽  
Nitric Oxide Release ◽  
Fibronectin Matrix ◽  
Pdl Cells ◽  
Fibronectin Fragments ◽  
Infection And Inflammation ◽  
Ifn Γ

ABSTRACT During infection and inflammation, bacterial and inflammatory proteases break down extracellular matrices into macromolecular fragments. Fibronectin fragments are associated with disease severity in arthritis and periodontitis. The mechanisms by which these fragments contribute to disease pathogenesis are unclear. One likely mechanism is that fibronectin fragments induce apoptosis of resident cells, which can be further modulated by nitric oxide. Nitric oxide levels are increased at inflammatory sites in periodontitis patients. The aim of this study was to examine whether a proapoptotic fibronectin matrix (AFn) exerts its action by inducing nitric oxide and whether priming by bacterial and inflammatory components exacerbates this mechanism. Our data demonstrate that AFn increased the levels of nitric oxide and inducible nitric oxide synthase (iNOS) dose and time dependently in periodontal ligament (PDL) cells. These effects and apoptosis were inhibited by iNOS suppression and enhanced by iNOS overexpression. Nitric oxide and iNOS induction were paralleled by increased c-Jun N-terminal kinase 1 (JNK-1) phosphorylation. JNK-1 overexpression enhanced the expression of nitric oxide and iNOS, whereas inhibiting JNK-1 by small interfering RNA or a kinase mutant reversed these findings. Priming PDL cells with Porphyromonas gingivalis, its lipopolysaccharide (LPS), or gamma interferon (IFN-γ) further increased nitric oxide levels and apoptosis. Escherichia coli and Streptococcus mutans induced lesser effects. Gingival fibroblasts and neutrophils responded to a lesser degree to these stimuli, whereas keratinocytes were resistant to apoptosis. Thus, proapoptotic matrices trigger nitric oxide release via JNK-1, promoting further apoptosis in host cells. LPS and IFN-γ accentuate this mechanism, suggesting that during inflammation, the affected matrices and bacterial and inflammatory components combined exert a greater pathogenic effect on host cells.

scholarly journals Interleukin-18 and Gamma Interferon Production by Oral Epithelial Cells in Response to Exposure to Candida albicans or Lipopolysaccharide Stimulation

2002 ◽  
Vol 70 (12) ◽  
pp. 7073-7080 ◽  
Author(s):  
Mahmoud Rouabhia ◽  
Geneviève Ross ◽  
Nathalie Pagé ◽  
Jamila Chakir
Keyword(s):  
Candida Albicans ◽  
Epithelial Cells ◽  
Early Stage ◽  
Oral Candidiasis ◽  
Gamma Interferon ◽  
Interleukin 18 ◽  
Dimorphic Fungus ◽  
Oral Epithelial Cells ◽  
Ifn Γ ◽  
Oral Epithelial

ABSTRACT Oral candidiasis is a collective name for a group of disorders caused by the dimorphic fungus Candida albicans. Host defenses against C. albicans essentially fall into two categories: specific immune mechanisms and local oral mucosal epithelial cell defenses. Since oral epithelial cells secrete a variety of cytokines and chemokines in response to oral microorganisms and since C. albicans is closely associated with oral epithelial cells as a commensal organism, we wanted to determine whether interleukin-18 (IL-18) and gamma interferon (IFN-γ) were produced by oral epithelial cells in response to C. albicans infection and lipopolysaccharide (LPS) stimulation. Our results showed that IL-18 mRNA and protein were constitutively expressed by oral epithelial cells and were down-regulated by Candida infections but increased following LPS stimulation. Both C. albicans and LPS significantly decreased pro-IL-18 (24 kDa) levels and increased active IL-18 (18 kDa) levels. This effect was IL-1β-converting-enzyme dependent. The increase in active IL-18 protein levels promoted the production of IFN-γ by infected cells. No effect was obtained with LPS. Although produced only at an early stage, secreted IFN-γ seemed to be a preferential response by oral epithelial cells to C. albicans growth. These results provide additional evidence for the contribution of oral epithelial cells to local (direct contact) and systemic (IL-18 and IFN-γ production) defense against exogenous stimulation such as C. albicans infection or LPS stimulation.

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