Peptidoglycan and Lipoteichoic Acid from Staphylococcus aureus Induce Tumor Necrosis Factor Alpha, Interleukin 6 (IL-6), and IL-10 Production in Both T Cells and Monocytes in a Human Whole Blood Model

ABSTRACT We have examined the ability of peptidoglycan (PepG) and lipoteichoic acid (LTA) isolated from Staphylococcus aureusto induce the release of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-10 in whole human blood and identified the cellular origins of these cytokines. Both PepG and LTA induced transient increases in TNF-α and IL-10 in plasma, with peak values at 6 and 12 h, respectively. IL-6 values increased throughout the experimental period (24 h). The TNF-α, IL-6, and IL-10 release induced by PepG and LTA was dose dependent. Only PepG was a potent inducer of TNF-α secretion. After stimulation of whole blood with PepG or LTA, very pure populations of monocytes (CD14 positive), T cells (CD2 positive), B cells (CD19 positive), and granulocytes (CD15 positive) were isolated by immunomagnetic separation and analyzed by reverse transcription-PCR for mRNA transcripts encoding TNF-α, IL-6, and IL-10. The TNF-α mRNA results were inconclusive. In contrast, PepG induced IL-6 and IL-10 mRNA accumulation in both T cells and monocytes. LTA, as well as lipopolysaccharide, induced IL-6 and IL-10 mRNA production in monocytes and possibly in T cells. Whether granulocytes and B cells produce cytokines in response to bacterial stimuli remains obscure. Blockade of the CD14 receptors with monoclonal antibodies (18D11) had no influence on the PepG-induced release of TNF-α but attenuated the LTA-induced release of the same cytokine. In conclusion, our data indicate that circulating T cells and monocytes contribute to cytokine production in sepsis caused by gram-positive bacteria.

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Effects of Tumor Necrosis Factor Alpha on Dendritic Cell Accumulation in Lymph Nodes Draining the Immunization Site and the Impact on the Anticryptococcal Cell-Mediated Immune Response

Infection and Immunity ◽

10.1128/iai.71.1.68-74.2003 ◽

2003 ◽

Vol 71 (1) ◽

pp. 68-74 ◽

Cited By ~ 55

Author(s):

Sean K. Bauman ◽

Gary B. Huffnagle ◽

Juneann W. Murphy

Keyword(s):

T Cells ◽

Tumor Necrosis Factor ◽

Lymph Nodes ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Delayed Type Hypersensitivity ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor

ABSTRACT Cell-mediated immune (CMI) responses and tumor necrosis factor alpha (TNF-α) have been shown to be essential in acquired protection against Cryptococcus neoformans. Induction of a protective anticryptococcal CMI response includes increases in dendritic cells (DC) and activated CD4+ T cells in draining lymph nodes (DLN). During the expression phase, activated CD4+ T cells accumulate at a peripheral site where cryptococcal antigen is injected, resulting in a classical delayed-type hypersensitivity (DTH) reaction. Induction of a nonprotective anticryptococcal CMI response results in no significant increases in the numbers of DC or activated CD4+ T cells in DLN. This study focuses on examining the role of TNF-α in induction of protective and nonprotective anticryptococcal CMI responses. We found that neutralization of TNF-α at the time of immunization with the protective immunogen (i) reduces the numbers of Langerhans cells, myeloid and lymphoid DC, and activated CD4+ T cells in DLN and (ii) diminishes the total numbers of cells, the numbers of activated CD4+ T cells, and amount of gamma interferon at the DTH reaction site. Although TNF-α neutralization during induction of the nonprotective CMI response had little effect on cellular and cytokine parameters measured, it did cause a reduction in footpad swelling when mice received challenge in the footpad. Our findings show that TNF-α functions during induction of the protective CMI response by influencing the accumulation of all three DC subsets into DLN. Without antigen stimulated DC in DLN, activated CD4+ T cells are not induced and thus not available for the expression phase of the CMI response.

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

Ophthalmic Research ◽

10.1159/000513586 ◽

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.

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

Molecular and Cellular Biology ◽

10.1128/mcb.01117-15 ◽

2016 ◽

Vol 36 (9) ◽

pp. 1342-1353 ◽

Cited By ~ 10

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.

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

Molecular and Cellular Biology ◽

10.1128/mcb.01538-06 ◽

2006 ◽

Vol 26 (24) ◽

pp. 9244-9255 ◽

Cited By ~ 43

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.

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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

Infection and Immunity ◽

10.1128/iai.69.11.7169-7172.2001 ◽

2001 ◽

Vol 69 (11) ◽

pp. 7169-7172 ◽

Cited By ~ 37

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.

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

Infection and Immunity ◽

10.1128/iai.69.8.4823-4830.2001 ◽

2001 ◽

Vol 69 (8) ◽

pp. 4823-4830 ◽

Cited By ~ 62

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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In silico studies for the interaction of tumor necrosis factor-alpha (TNF-α) with different saponins from Vietnamese ginseng (Panax vietnamesis)

Biophysics and Physicobiology ◽

10.2142/biophysico.13.0_173 ◽

2016 ◽

Vol 13 (0) ◽

pp. 173-180 ◽

Cited By ~ 6

Author(s):

Oanh T. P. Kim ◽

Manh D. Le ◽

Hoang X. Trinh ◽

Hai V. Nong

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

In Silico ◽

Tumor Necrosis ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor

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

Infection and Immunity ◽

10.1128/iai.69.5.2847-2852.2001 ◽

2001 ◽

Vol 69 (5) ◽

pp. 2847-2852 ◽

Cited By ~ 18

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.

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