scholarly journals Enhancement of Mycobacterium tuberculosis-Induced Tumor Necrosis Factor Alpha Production from Primary Human Monocytes by an Activated T-Cell Membrane-Mediated Mechanism

2001 ◽  
Vol 69 (11) ◽  
pp. 6580-6587 ◽  
Author(s):  
Jan Warwick-Davies ◽  
Amanda J. Watson ◽  
George E. Griffin ◽  
Sanjeev Krishna ◽  
Robin J. Shattock
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Human Monocytes ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Mycobacterium tuberculosis alone induces small, donor-variable amounts of tumor necrosis factor alpha (TNF-α) from primary human monocytes in vitro. However, TNF-α release is increased 5- to 500-fold when fixed activated T cells (FAT) or their isolated, unfixed membranes are added to this system. This FAT-induced synergy was at least as potent as that induced by gamma interferon (IFN-γ) at 100 U/ml. FAT-enhanced TNF-α production is at least in part transcriptionally mediated, as reflected by quantitative changes in TNF-α mRNA between 2 and 6 h poststimulation. Unlike IFN-γ-cocultured cells, FAT-treated monocytes appeared not to have enhanced TNF-α message stability, suggesting that de novo transcription may be involved in this effect. Furthermore, M. tuberculosis alone induced only minimal DNA binding of monocyte NF-κB, but cells treated with M. tuberculosis and FAT potentiated NF-κB activity more effectively. It is therefore possible that one mechanism by which FAT synergize with M. tuberculosis to stimulate TNF-α production is via NF-κB-enhanced transcription. These data strongly suggest that in the interaction of cells involved in the immune response to M. tuberculosis, T-cell stimulation of monocyte TNF-α production involves a surface membrane interaction(s) as well as soluble mediators.

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 Destructive Arthritis in Vaccinated Interferon Gamma-Deficient Mice Challenged with Borrelia burgdorferi: Modulation by Tumor Necrosis Factor Alpha

2003 ◽  
Vol 10 (1) ◽  
pp. 44-52 ◽  
Author(s):  
John A. Christopherson ◽  
Erik L. Munson ◽  
Douglas M. England ◽  
Cindy L. Croke ◽  
Monica C. Remington ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Borrelia Burgdorferi ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Deficient Mice ◽  
Necrosis Factor

ABSTRACT We found that Borrelia burgdorferi-vaccinated gamma interferon-deficient (IFN-γ0) mice challenged with B. burgdorferi developed prominent chronic destructive osteoarthropathy. When these mice were treated with anti-tumor necrosis factor alpha (TNF-α) antibody, the severity of the destructive osteoarthritis was enhanced and affected the mobility of the animals. In addition, extensive swelling of the hind paws occurred. In contrast, treatment of B. burgdorferi-vaccinated, challenged IFN-γ0 mice with recombinant TNF-α (rTNF-α) inhibited the development of arthritis, including swelling of the hind paws. Moreover, treatment of vaccinated, challenged IFN-γ0 mice with anti-TNF-α inhibited fourfold the production of an antibody that kills B. burgdorferi, while treatment of vaccinated, challenged IFN-γ0 mice with rTNF-α slightly elevated the level of the borreliacidal antibody. These results suggest that the level of TNF-α directly or indirectly regulates the production of borreliacidal antibody and the development of vaccine-induced destructive Lyme osteoarthritis. Studies are in progress to determine the mechanism by which TNF-α-dependent cytokines generate the destructive arthritis.

scholarly journals Placental Tumor Necrosis Factor Alpha but Not Gamma Interferon Is Associated with Placental Malaria and Low Birth Weight in Malawian Women

2003 ◽  
Vol 71 (1) ◽  
pp. 267-270 ◽  
Author(s):  
Stephen J. Rogerson ◽  
Heidi C. Brown ◽  
Elena Pollina ◽  
Elizabeth T. Abrams ◽  
Eyob Tadesse ◽  
...  
Keyword(s):  
Birth Weight ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Placental Blood ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Malaria in pregnancy predisposes to maternal anemia and low birth weight (LBW). We examined the possible roles of the cytokines tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) in these adverse outcomes. We measured cytokine concentrations in placental, peripheral, and cord blood plasma in relation to malaria parasitemia and placental monocyte accumulation in 276 Malawian women. Maternal hemoglobin concentration, human immunodeficiency virus status, and infant birth weight were determined. Concentrations of TNF-α in placental blood were correlated with densities of Plasmodium falciparum-infected erythrocytes (P < 0.0001) and of intervillous monocyte infiltrates (P < 0.0001) on placental histology. Peripheral blood TNF-α concentrations were relatively low and were weakly associated with malaria. TNF-α concentrations were higher in placental blood, where they were strongly associated with malaria. Placental plasma TNF-α levels were higher in women who had LBW babies (P = 0.0027), women with febrile symptoms (P < 0.0001), and teenage mothers (P = 0.04) than in other women. The presence of TNF-α in cord blood was not associated with malaria infection. IFN-γ levels were infrequently elevated, and elevated IFN-γ levels were not associated with poor pregnancy outcomes. Placental production of TNF-α, but not of IFN-γ, may be implicated in impaired fetal growth in Malawian women.

scholarly journals Interaction of the CD43 Sialomucin with the Mycobacterium tuberculosis Cpn60.2 Chaperonin Leads to Tumor Necrosis Factor Alpha Production

2017 ◽  
Vol 85 (3) ◽  
Author(s):  
Alvaro Torres-Huerta ◽  
Tomás Villaseñor ◽  
Angel Flores-Alcantar ◽  
Cristina Parada ◽  
Estefanía Alemán-Navarro ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Mycobacterium tuberculosis is the causal agent of tuberculosis. Tumor necrosis factor alpha (TNF-α), transforming growth factor β (TGF-β), and gamma interferon (IFN-γ) secreted by activated macrophages and lymphocytes are considered essential to contain Mycobacterium tuberculosis infection. The CD43 sialomucin has been reported to act as a receptor for bacilli through its interaction with the chaperonin Cpn60.2, facilitating mycobacterium-macrophage contact. We report here that Cpn60.2 induces both human THP-1 cells and mouse-derived bone marrow-derived macrophages (BMMs) to produce TNF-α and that this production is CD43 dependent. In addition, we present evidence that the signaling pathway leading to TNF-α production upon interaction with Cpn60.2 requires active Src family kinases, phospholipase C-γ (PLC-γ), phosphatidylinositol 3-kinase (PI3K), p38, and Jun N-terminal protein kinase (JNK), both in BMMs and in THP-1 cells. Our data highlight the role of CD43 and Cpn60.2 in TNF-α production and underscore an important role for CD43 in the host-mycobacterium interaction.

scholarly journals Mannose-Capped Lipoarabinomannan from Mycobacterium tuberculosis Induces Soluble Tumor Necrosis Factor Receptor Production through Tumor Necrosis Factor Alpha-Converting Enzyme Activation

2012 ◽  
Vol 80 (11) ◽  
pp. 3858-3868 ◽  
Author(s):  
Jillian M. Richmond ◽  
Elizabeth R. Duffy ◽  
Jinhee Lee ◽  
Kavon Kaboli ◽  
Daniel G. Remick ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Converting Enzyme ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACTPrimaryMycobacterium tuberculosisinfection results in granuloma formation in lung tissue. A granuloma encapsulates mycobacterium-containing cells, thereby preventing dissemination and further infection. Tumor necrosis factor alpha (TNF-α) is a host-protective cytokine duringM. tuberculosisinfection due to its role in promoting and sustaining granuloma formation. TNF activity is regulated through the production of soluble TNF receptors (sTNFRI and sTNFRII). Therefore, we examined the potential production of endogenous sTNFRs duringM. tuberculosisinfection. Using the murine model of aerosolM. tuberculosisinfection, we determined that levels of sTNFR production were elevated in bronchoalveolar lavage fluid 1 month following infection. An investigation ofM. tuberculosiscell wall components identified that the known virulence factor mannose-capped lipoarabinomannan (ManLAM) was sufficient to induce sTNFR production, with sTNFRII being produced preferentially compared with sTNFRI. ManLAM stimulated the release of sTNFRs without TNF production, which corresponded to an increase in TNF-α-converting enzyme (TACE) activity. To determine the relevance of these findings, serum samples fromM. tuberculosis-infected patients were tested and found to have an increase in the sTNFRII/sTNFRI ratio. These data identify a mechanism by whichM. tuberculosisinfection can promote the neutralization of TNF and furthermore suggest the potential use of the sTNFRII/sTNFRI ratio as an indicator of tuberculosis disease.

scholarly journals Local Role for Tumor Necrosis Factor Alpha in the Pulmonary Inflammatory Response to Mycobacterium tuberculosis Infection

2002 ◽  
Vol 70 (4) ◽  
pp. 2082-2089 ◽  
Author(s):  
Sherilyn Smith ◽  
Denny Liggitt ◽  
Elizabeth Jeromsky ◽  
Xiaoxia Tan ◽  
Shawn J. Skerrett ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tumor Necrosis Factor ◽  
Inflammatory Response ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Gamma Interferon ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT The local intrapulmonary role of tumor necrosis factor alpha (TNF-α) in a protective host response during acute and chronic infection with Mycobacterium tuberculosis is incompletely understood. To directly assess its role in the intrapulmonary immune response, we compared the responses of transgenic mice with a local pulmonary blockade of TNF-α (SPCTNFRIIFc mice) to mice with globally inhibited TNF-α (TNFRKO mice) and mice with normal immune systems (control mice). Consistent with previous reports, 100% of TNFRKO mice died by 28 days after aerosol infection, and these mice had markedly increased numbers of bacteria and widespread tissue necrosis in their lungs compared to controls. The median survival time of the SPCTNFRIIFc mice was 142 days, and 75% died by 180 days. Even though the numbers of bacteria in the lungs of the SPCTNFRIIFc mice were marginally increased compared to controls, these mice had a persistent neutrophilic inflammatory response and increased expression of proinflammatory cytokines (interleukin-1α/β [IL-1α/β], IL-18, gamma interferon, IL-6, and macrophage migration inhibitory factor) and chemokines (eotaxin, macrophage inflammatory protein 1α/β, gamma interferon-inducible protein 10, macrophage chemotaxic protein 1, and TCA-3) in their lungs. These studies with the SPCTNFRIIFc mice provide direct evidence for the local importance of TNF-α in the proper regulation of host defense to M. tuberculosis. The studies also suggest that when the local actions of TNF-α are selectively impaired in the lungs, tissue destruction and death ensue, at least in part, due to persistent expression of proinflammatory mediators that would normally be downregulated.

Association of interferon-gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) polymorphisms with susceptibility to vitiligo in Iranian patients

2011 ◽  
Vol 44 (13) ◽  
pp. S298
Author(s):  
Faryabi Mohamad Reza ◽  
Kamali-Sarvestani Eskandar ◽  
Namian Ali-Mohammad ◽  
Shahbaz Shima ◽  
Salmanpoor Rahmatolah
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Interferon Gamma ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor ◽  
Iranian Patients

Erythromycin Inhibition of Lipopolysaccharide-Stimulated Tumor Necrosis Factor Alpha Production by Human Monocytes in Vitro

1992 ◽  
Vol 101 (10_suppl) ◽  
pp. 16-20 ◽  
Author(s):  
Yukiko Iino ◽  
Minoru Toriyama ◽  
Yasuhiro Natori ◽  
Koichiro Kudo ◽  
Akira Yuo
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Penicillin G ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

The mechanism of clinical effectiveness of low-dose and long-term erythromycin (EM) treatment for diffuse panbronchiolitis, sinobronchial syndrome, and associated otitis media with effusion was investigated by studying the effects of EM on tumor necrosis factor alpha (TNF-α) production by cultured human monocytes stimulated with lipopolysaccharide. At concentrations of 0.1 μg/mL or more, EM inhibited TNF-α release from human monocytes stimulated by lipopolysaccharide in a dose-dependent manner. Of the other macrolides tested, roxithromycin, an EM derivative, also showed significant inhibition of TNF-α production, whereas josamycin failed to inhibit TNF-α release from monocytes. Nonmacrolidic drugs such as minocycline hydrochloride, ofloxacin, or penicillin G had no significant effect on TNF-α production. These results suggest that the clinical improvement of chronic respiratory diseases by EM may depend on the suppression of production of inflammatory cytokines such as TNF-α.

scholarly journals Tumor Necrosis Factor Alpha-Mediated Toxic Shock inTrypanosoma cruzi-Infected Interleukin 10-Deficient Mice

2000 ◽  
Vol 68 (7) ◽  
pp. 4075-4083 ◽  
Author(s):  
Christoph Hölscher ◽  
Markus Mohrs ◽  
Wen Juan Dai ◽  
Gabriele Köhler ◽  
Bernhard Ryffel ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 10 ◽  
Toxic Shock ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Using interleukin-10 (IL-10)-deficient (IL-10−/−) mice, previous studies revealed a pathological immune response after infection with Trypanosoma cruzi that is associated with CD4+ T cells and overproduction of proinflammatory cytokines. In this study we further investigate the pathology and potential mediators for the mortality in infected animals. T. cruzi-infected IL-10−/− mice showed reduced parasitemia accompanied by increased systemic release of gamma interferon (IFN-γ), IL-12, and reactive nitrogen intermediates and overproduction of tumor necrosis factor alpha (TNF-α). Despite this early resistance, IL-10−/− mice died within the third week of infection, whereas all control mice survived acute infection. The clinical manifestation with weight loss, hypothermia, hypoglycemia, hyperkalemia, and increased liver-derived enzymes in the blood together with hepatic necrosis and intravascular coagulation in moribund mice indicated a toxic shock-like syndrome, possibly mediated by the systemic TNF-α overproduction. Indeed, high production of systemic TNF-α significantly correlated with mortality, and moribund mice died with critically high TNF-α concentrations in the blood. Consequent treatment with anti-TNF-α antiserum attenuated pathological changes in T. cruzi-infected IL-10−/− mice and significantly prolonged survival; the mice died during the fourth week postinfection, again with a striking correlation between regaining high systemic TNF-α concentrations and the time of death. Since elevated serum IL-12 and IFN-γ concentrations were not affected by the administration of antiserum, these studies suggest that TNF-α is the direct mediator of this toxic shock syndrome. In conclusion, induction of endogenous IL-10 during experimentally induced Chagas' disease seems to be crucial for counterregulating an overshooting proinflammatory cytokine response resulting in TNF-α-mediated toxic shock.

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