scholarly journals Induction of Interleukin-4 (IL-4) by Legionella pneumophila Infection in BALB/c Mice and Regulation of Tumor Necrosis Factor Alpha, IL-6, and IL-1β

2000 ◽  
Vol 68 (9) ◽  
pp. 5234-5240 ◽  
Author(s):  
Catherine Newton ◽  
Shannon McHugh ◽  
Ray Widen ◽  
Noriya Nakachi ◽  
Thomas Klein ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Legionella Pneumophila ◽  
Tumor Necrosis ◽  
Ex Vivo ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Deficient Mice ◽  
Necrosis Factor

ABSTRACT Infection of BALB/c mice with a sublethal concentration ofLegionella pneumophila causes an acute disease that is resolved by innate immune responses. The infection also initiates the development of adaptive Th1 responses that protect the mice from challenge infections. To study the early responses, cytokines induced during the first 24 h after infection were examined. In the serum, interleukin-12 (IL-12) was detectable by 3 h and peaked at 10 h, while gamma interferon was discernible by 5 h and peaked at 8 h. Similar patterns were observed in ex vivo cultures of splenocytes. A transient IL-4 response was also detected by 3 h postinfection in ex vivo cultures. BALB/c IL-4-deficient mice were more susceptible to L. pneumophila infection than were wild-type mice. The infection induced higher serum levels of acute-phase cytokines (tumor necrosis factor alpha [TNF-α], IL-1β, and IL-6), and reducing TNF-α levels with antibodies protected the mice from death. Moreover, the addition of IL-4 to L. pneumophila-infected macrophage cultures suppressed the production of these cytokines. Thus, the lack of IL-4 in the deficient mice resulted in unchecked TNF-α production, which appeared to cause the mortality. Monocyte chemoattractant protein-1 (MCP-1), a chemokine that is induced by IL-4 during Listeria monocytogenesinfection, was detected at between 2 and 30 h after infection. However, MCP-1 did not appear to be induced by IL-4 or to be required for the TNF-α regulation by IL-4. The data suggest that the early increase in IL-4 serves to regulate the mobilization of acute phase cytokines and thus controls the potential harmful effects of these cytokines.

scholarly journals Endogenous Interleukin-6 Plays a Crucial Protective Role in Streptococcal Toxic Shock Syndrome via Suppression of Tumor Necrosis Factor Alpha Production

2005 ◽  
Vol 73 (6) ◽  
pp. 3745-3748 ◽  
Author(s):  
Hongyan Diao ◽  
Masashi Kohanawa
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Interleukin 6 ◽  
Tumor Necrosis ◽  
Protective Role ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Deficient Mice ◽  
Necrosis Factor

ABSTRACT During a Streptococcus pyogenes infection in interleukin-6 (IL-6)-deficient mice, there is elevation of serum tumor necrosis factor alpha (TNF-α) levels, muscular necrosis, and death compared with infection of C57BL/6 mice. Anti-TNF-α monoclonal antibody treatment decreased mortality and muscular necrosis in the infected IL-6-deficient mice. These results suggest that IL-6 plays a crucial protective role via suppression of TNF-α production in S. pyogenes infection.

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 Critical Role of the Complement System in Group B Streptococcus-Induced Tumor Necrosis Factor Alpha Release

2003 ◽  
Vol 71 (11) ◽  
pp. 6344-6353 ◽  
Author(s):  
Ofer Levy ◽  
Rochelle M. Jean-Jacques ◽  
Colette Cywes ◽  
Richard B. Sisson ◽  
Kol A. Zarember ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Alternative Pathway ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Group B ◽  
Deficient Mice ◽  
Necrosis Factor

ABSTRACT Group B Streptococcus (GBS) is a major cause of newborn sepsis and meningitis and induces systemic release of tumor necrosis factor alpha (TNF-α), believed to play a role in morbidity and mortality. While previous studies have shown that GBS can induce TNF-α release from monocytes and macrophages, little is known about the potential modulating effect of plasma or serum on GBS-induced TNF-α release, and there are conflicting reports as to the host receptors involved. In a human whole-blood assay system, GBS type III COH-1 potently induced substantial monocyte TNF-α release in adult peripheral blood and, due to a higher concentration of monocytes, 10-fold-greater TNF-α release in newborn cord blood. Remarkably, GBS-induced TNF-α release from human monocytes was enhanced ∼1,000-fold by heat-labile serum components. Experiments employing C2-, C3-, or C7-depleted serum demonstrated that C3 activation via the alternative pathway is crucial for potent GBS-induced TNF-α release. Accordingly, whole blood from C3-deficient mice demonstrated significantly reduced GBS-induced TNF-α release. Preincubation with human serum enhanced the TNF-α-inducing activity of GBS in a C3- and factor B-dependent manner, implying deposition of complement components via the alternative pathway. GBS-induced TNF-α release was inhibited by monoclonal antibodies directed against each of the components of CR3 and CR4: the common integrin β subunit CD18 and the α subunits CD11b (of CR3) and CD11c (of CR4). Blood derived from CR3 (CD11b/CD18)-deficient mice demonstrated a markedly diminished TNF-α response to GBS. We conclude that the ability of plasma and serum to greatly amplify GBS-induced TNF-α release reflects the activity of the alternative complement pathway that deposits fragments on GBS and thereby enhances CR3- and CR4-mediated monocyte activation.

scholarly journals Tumor Necrosis Factor Alpha Receptor I Is Important for Survival from Streptococcus pneumoniaeInfections

1999 ◽  
Vol 67 (2) ◽  
pp. 595-601 ◽  
Author(s):  
David P. O’Brien ◽  
David E. Briles ◽  
Alexander J. Szalai ◽  
Anh-Hue Tu ◽  
Inaki Sanz ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Acute Phase ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
P75 Receptor ◽  
Deficient Mice ◽  
Necrosis Factor

ABSTRACT Tumor necrosis factor alpha (TNF-α) is important in resistance to various microorganisms and provides signals to the target cells through two different receptors, TNF-α receptor I (TNFRI) (p55 receptor) and TNFRII (p75 receptor). To delineate the significance of the two different signaling pathways in resisting infections with extracellular bacteria, we examined the resistance of mice to Streptococcus pneumoniae (serotype 6B). TNF-α needs to be present early in infections, since one injection of wild-type mice with anti-TNF-α leads to an increased susceptibility of these mice to S. pneumoniae. TNF-α signaling through the p55 receptor (but not the p75 receptor) is crucial in resisting S. pneumoniae infections, because intraperitoneal injection of 100 CFU/mouse killed p55-deficient mice by day 2 of infection, whereas 1,000,000 CFU/mouse was needed to kill half of the control mice. p55-deficient mice do not show evidence of a deficient acute-phase response. All three types of mice (p55 deficient, p75 deficient, and normal) showed comparable rises in the levels of two acute-phase proteins (serum amyloid P and C3) at 24, 48, and 72 h after the experimental infections, and all of the mice showed comparable influxes of neutrophils to the site of infection. Finally, it was demonstrated that p55-deficient mice can be protected from the lethal effects of S. pneumoniae infection by injection of antibodies specific for S. pneumoniaepolysaccharide capsule.

scholarly journals Association of tumor necrosis factor-alpha -308 G/A and -238 G/A polymorphism with diabetic retinopathy: a systematic review and updated meta-analysis.

2020 ◽  
Author(s):  
Wenna Gao ◽  
Ruilin Zhu ◽  
liu yang
Keyword(s):  
Diabetic Retinopathy ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Meta Analysis ◽  
Entire Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Background: Mounting evidence has suggested tumor necrosis factor-alpha (TNF-α) can promote the development of diabetic retinopathy (DR), and TNF-α gene variants may influence DR risk. However, the results are quite different. Objectives: To comprehensively address this issue, we performed the meta-analysis to evaluate the association of TNF-α-308 G/A and -238 G/A polymorphism with DR. Method: Data were retrieved in a systematic manner and analyzed using STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Allelic and genotypic comparisons between cases and controls were evaluated. Results: For the TNF-α-308 G/A polymorphism, overall analysis suggested a marginal association with DR [the OR(95%CI) of (GA versus GG), (GA + AA) versus GG, and (A versus G) are 1.21(1.04, 1.41), 1.20(1.03, 1.39), and 1.14(1.01, 1.30), respectively]. And the subgroup analysis indicated an enhanced association among the European population. For the TNF-α-238 G/A polymorphism, there was mild correlation in the entire group [the OR(95%CI) of (GA versus GG) is 1.55(1.14,2.11) ], which was strengthened among the Asian population. Conclusion: The meta-analysis suggested that -308 A and -238 A allele in TNF-α gene potentially increased DR risk and showed a discrepancy in different ethnicities.

scholarly journals Analysis of Subcellular RNA Fractions Revealed a Transcription-Independent Effect of Tumor Necrosis Factor Alpha on Splicing, Mediated by Spt5

2016 ◽  
Vol 36 (9) ◽  
pp. 1342-1353 ◽  
Author(s):  
Gil Diamant ◽  
Tal Eisenbaum ◽  
Dena Leshkowitz ◽  
Rivka Dikstein
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Independent Effect ◽  
Necrosis Factor Alpha ◽  
Pol Ii ◽  
Tnf Α ◽  
Factor Alpha ◽  
Induced Genes ◽  
Necrosis Factor

The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) modulates the expression of many genes, primarily through activation of NF-κB. Here, we examined the global effects of the elongation factor Spt5 on nascent and mature mRNAs of TNF-α-induced cells using chromatin and cytosolic subcellular fractions. We identified several classes of TNF-α-induced genes controlled at the level of transcription, splicing, and chromatin retention. Spt5 was found to facilitate splicing and chromatin release in genes displaying high induction rates. Further analysis revealed striking effects of TNF-α on the splicing of 25% of expressed genes; the vast majority were not transcriptionally induced. Splicing enhancement of noninduced genes by TNF-α was transient and independent of NF-κB. Investigating the underlying basis, we found that Spt5 is required for the splicing facilitation of the noninduced genes. In line with this, Spt5 interacts with Sm core protein splicing factors. Furthermore, following TNF-α treatment, levels of RNA polymerase II (Pol II) but not Spt5 are reduced from the splicing-induced genes, suggesting that these genes become enriched with a Pol II-Spt5 form. Our findings revealed the Pol II-Spt5 complex as a highly competent coordinator of cotranscriptional splicing.

scholarly journals HSP70 Induction by ING Proteins Sensitizes Cells to Tumor Necrosis Factor Alpha Receptor-Mediated Apoptosis

2006 ◽  
Vol 26 (24) ◽  
pp. 9244-9255 ◽  
Author(s):  
Xiaolan Feng ◽  
Shirin Bonni ◽  
Karl Riabowol
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Kinase Inhibitor ◽  
Heat Shock Gene ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Primary Fibroblasts ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT ING proteins affect apoptosis, growth, and DNA repair by transducing stress signals such as DNA damage, binding histones, and subsequently regulating chromatin structure and p53 activity. p53 target genes, including the p21 cyclin-dependent kinase inhibitor and Bax, an inducer of apoptosis, are regulated by ING proteins. To identify additional targets downstream of p33ING1 and p32ING2, cDNA microarrays were performed on phenotypically normal human primary fibroblasts. The 0.36% of genes affected by ING proteins in primary fibroblasts were distinct from targets seen in established cells and included the HSP70 heat shock gene, whose promoter was specifically induced >10-fold. ING1-induced expression of HSP70 shifted cells from survival to a death pathway in response to tumor necrosis factor alpha (TNF-α), and p33ING1b protein showed synergy with TNF-α in inducing apoptosis, which correlated with reduced NF-κB-dependent transcription. These findings are consistent with previous reports that HSP70 promotes TNF-α-mediated apoptosis by binding I-κΒ kinase gamma and impairing NF-κB survival signaling. Induction of HSP70 required the amino terminus of ING1b but not the plant homeodomain region that was recently identified as a histone binding domain. Regulation of HSP70 gene expression by the ING tumor suppressors provides a novel link between the INGs and the stress-regulated NF-κB survival pathway important in hypoxia and angiogenesis.

scholarly journals Comparative Analysis of Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Activity in Serum and Lethality in Mice and Rabbits Pretreated with the Staphylococcal Superantigen Toxic Shock Syndrome Toxin 1

2001 ◽  
Vol 69 (11) ◽  
pp. 7169-7172 ◽  
Author(s):  
Martin M. Dinges ◽  
Patrick M. Schlievert
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Host Susceptibility ◽  
Necrosis Factor Alpha ◽  
Lethal Effects ◽  
Tnf Α ◽  
Factor Alpha ◽  
Toxic Shock Syndrome Toxin ◽  
Necrosis Factor

ABSTRACT Host susceptibility to lipopolysaccharide (LPS) is correlated with the levels of circulating tumor necrosis factor alpha (TNF-α) that develop in response to circulating LPS. Mice are resistant, relative to rabbits, to the lethal effects of LPS. This study indicates that mice and rabbits are equally sensitive to the lethal effects of circulating TNF-α but that mice are more resistant than rabbits to the induction of circulating TNF-α by LPS.

scholarly journals Major Outer Membrane Protein Omp25 of Brucella suis Is Involved in Inhibition of Tumor Necrosis Factor Alpha Production during Infection of Human Macrophages

2001 ◽  
Vol 69 (8) ◽  
pp. 4823-4830 ◽  
Author(s):  
Véronique Jubier-Maurin ◽  
Rose-Anne Boigegrain ◽  
Axel Cloeckaert ◽  
Antoine Gross ◽  
Maria-Teresa Alvarez-Martinez ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Macrophage Infection ◽  
Necrosis Factor Alpha ◽  
Human Macrophages ◽  
Tnf Α ◽  
Brucella Suis ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Brucella spp. can establish themselves and cause disease in humans and animals. The mechanisms by whichBrucella spp. evade the antibacterial defenses of their host, however, remain largely unknown. We have previously reported that live brucellae failed to induce tumor necrosis factor alpha (TNF-α) production upon human macrophage infection. This inhibition is associated with a nonidentified protein that is released into culture medium. Outer membrane proteins (OMPs) of gram-negative bacteria have been shown to modulate macrophage functions, including cytokine production. Thus, we have analyzed the effects of two major OMPs (Omp25 and Omp31) of Brucella suis 1330 (wild-type [WT] B. suis) on TNF-α production. For this purpose, omp25and omp31 null mutants of B. suis(Δomp25 B. suis and Δomp31 B. suis, respectively) were constructed and analyzed for the ability to activate human macrophages to secrete TNF-α. We showed that, in contrast to WTB. suis or Δomp31 B. suis, Δomp25 B. suis induced TNF-α production when phagocytosed by human macrophages. The complementation of Δomp25 B. suis with WT omp25 (Δomp25-omp25 B. suis mutant) significantly reversed this effect: Δomp25-omp25 B. suis-infected macrophages secreted significantly less TNF-α than did macrophages infected with the Δomp25 B. suismutant. Furthermore, pretreatment of WT B. suis with an anti-Omp25 monoclonal antibody directed against an epitope exposed at the surface of the bacteria resulted in substancial TNF-α production during macrophage infection. These observations demonstrated that Omp25 of B. suis is involved in the negative regulation of TNF-α production upon infection of human macrophages.

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