Effect of apigenin, kaempferol and resveratrol on the gene expression and protein secretion of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) in RAW-264.7 macrophages

ABSTRACT Interstitial pneumonia is a major clinical manifestation of primary or recurrent cytomegalovirus (CMV) infection in immunocompromised recipients of a bone marrow transplant. In a murine model, lungs were identified as a prominent site of CMV latency and recurrence. Pulmonary latency of murine CMV is characterized by high viral genome burden and a low incidence of variegated immediate-early (IE) gene expression, reflecting a sporadic activity of the major IE promoters (MIEPs) and enhancer. The enhancer-flanking promoters MIEP1/3 and MIEP2 are switched on and off during latency in a ratio of ∼2:1. MIEP1/3 latency-associated activity generates the IE1 transcript of the ie1/3 transcription unit but not the alternative splicing product IE3 that encodes the essential transactivator of early gene expression. Splicing thus appeared to be an important checkpoint for maintenance of latency. In accordance with previous work of others, we show here that signaling by the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) activates IE1/3 transcription in vivo. As an addition to current knowledge, Poisson distribution analysis revealed an increased incidence of IE1/3 transcriptional events as well as a higher amount of transcripts per event. Notably, TNF-α promoted the splicing to IE3 transcripts, but transcription did not proceed to the M55/gB early gene. Moreover, the activated transcriptional state induced by TNF-α did not predispose latently infected mice to a higher incidence of virus recurrence after hematoablative treatment. In conclusion, TNF-α is an important inductor of IE gene transcriptional reactivation, whereas early genes downstream in the viral replicative cycle appear to be the rate-limiting checkpoint(s) for virus recurrence.

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Regulation of Tumor Necrosis Factor Alpha Gene Expression by Mycobacteria Involves the Assembly of a Unique Enhanceosome Dependent on the Coactivator Proteins CBP/p300

Molecular and Cellular Biology ◽

10.1128/mcb.23.2.526-533.2003 ◽

2003 ◽

Vol 23 (2) ◽

pp. 526-533 ◽

Cited By ~ 63

Author(s):

Robert Barthel ◽

Alla V. Tsytsykova ◽

Amy K. Barczak ◽

Eunice Y. Tsai ◽

Christopher C. Dascher ◽

...

Keyword(s):

Gene Expression ◽

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Regulatory Elements ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor ◽

Stimulation Of

ABSTRACT Tumor necrosis factor alpha (TNF-α) plays an important role in host containment of infection by Mycobacterium tuberculosis, one of the leading causes of death by an infectious agent globally. Using the pathogenic M. tuberculosis strain H37Rv, we present evidence that upon stimulation of monocytic cells by M. tuberculosis a unique TNF-α enhanceosome is formed, and it is distinct from the TNF-α enhanceosome that forms in T cells stimulated by antigen engagement or virus infection. A distinct set of activators including ATF-2, c-jun, Ets, Sp1, Egr-1 and the coactivator proteins CBP/p300 are recruited to the TNF-α promoter after stimulation with M. tuberculosis. Furthermore, the formation of this enhanceosome is dependent on inducer-specific helical phasing relationships between transcription factor binding sites. We also show that the transcriptional activity of CBP/p300 is potentiated by mycobacterial stimulation of monocytes. The identification of TNF-α regulatory elements and coactivators involved in M. tuberculosis-stimulated gene expression thus provides potential selective molecular targets in the modulation of TNF-α gene expression in the setting of mycobacterial infection.

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Anemia and Interleukin-10, Tumor Necrosis Factor Alpha, and Erythropoietin Levels among Children with Acute, Uncomplicated Plasmodium falciparum Malaria

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.8.6.1164-1170.2001 ◽

2001 ◽

Vol 8 (6) ◽

pp. 1164-1170 ◽

Cited By ~ 32

Author(s):

Veronique Nussenblatt ◽

Gelasius Mukasa ◽

Amy Metzger ◽

Grace Ndeezi ◽

Elizabeth Garrett ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Geometric Mean ◽

Interleukin 10 ◽

Necrosis Factor Alpha ◽

Age Related ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor

ABSTRACT Anemia is an important complication of malaria, and its pathogenesis is not well understood. To gain insight into potential age-related relationships between tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), erythropoietin, and anemia during acute malaria, 273 children of ages 12 to 120 months presenting with acute, uncomplicated malaria in Kampala, Uganda, were monitored at enrollment and 3 and 7 days later. Younger children had higher geometric mean erythropoietin, TNF-α, and α1-acid glycoprotein (AGP) concentrations than older children. Univariate regression analysis revealed that age, log10 erythropoietin levels, IL-10/TNF-α ratio, and AGP levels were each significantly associated with hemoglobin levels at baseline. Hemoglobin concentrations were inversely correlated with the log10erythropoietin level at all three visits. For the older age groups, higher levels of TNF-α were significantly associated with higher IL-10 levels at all three visits, but this relationship was significant only at baseline for younger children. These data suggest that younger children do not maintain IL-10 production in response to the inflammatory process, and this mechanism may contribute to the more severe anemia found in younger children. Acute malaria is an illness whose incidence and severity are largely age dependent. Further studies are needed to understand the relationships between age-related immune responses to malaria and their role in the pathogenesis of malarial anemia.

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In VitroInfection of Bovine Monocytes with Mycoplasma bovis Delays Apoptosis and Suppresses Production of Gamma Interferon and Tumor Necrosis Factor Alpha but Not Interleukin-10

Infection and Immunity ◽

10.1128/iai.00961-13 ◽

2013 ◽

Vol 82 (1) ◽

pp. 62-71 ◽

Cited By ~ 35

Author(s):

Musa Mulongo ◽

Tracy Prysliak ◽

Erin Scruten ◽

Scott Napper ◽

Jose Perez-Casal

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Interleukin 10 ◽

Mycoplasma Bovis ◽

Blood Monocytes ◽

Necrosis Factor Alpha ◽

Content Type ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor

ABSTRACTMycoplasma bovisis one of the major causative pathogens of bovine respiratory complex disease (BRD), which is characterized by enzootic pneumonia, mastitis, pleuritis, and polyarthritis.M. bovisenters and colonizes bovine respiratory epithelial cells through inhalation of aerosol from contaminated air. The nature of the interaction betweenM. bovisand the bovine innate immune system is not well understood. We hypothesized thatM. bovisinvades blood monocytes and regulates cellular function to support its persistence and systemic dissemination. We used bovine-specific peptide kinome arrays to identify cellular signaling pathways that could be relevant toM. bovis-monocyte interactionsin vitro. We validated these pathways using functional, protein, and gene expression assays. Here, we show that infection of bovine blood monocytes withM. bovisdelays spontaneous or tumor necrosis factor alpha (TNF-α)/staurosporine-driven apoptosis, activates the NF-κB p65 subunit, and inhibits caspase-9 activity. We also report thatM. bovis-infected bovine monocytes do not produce gamma interferon (IFN-γ) and TNF-α, although the level of production of interleukin-10 (IL-10) is elevated. Our findings suggest thatM. bovistakes over the cellular machinery of bovine monocytes to prolong bacterial survival and to possibly facilitate subsequent systemic distribution.

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Tumor Necrosis Factor Alpha Induction of NF-κB Requires the Novel Coactivator SIMPL

Molecular and Cellular Biology ◽

10.1128/mcb.24.21.9317-9326.2004 ◽

2004 ◽

Vol 24 (21) ◽

pp. 9317-9326 ◽

Cited By ~ 19

Author(s):

Hyung-Joo Kwon ◽

Erin Haag Breese ◽

Eva Vig-Varga ◽

Yong Luo ◽

Younghee Lee ◽

...

Keyword(s):

Gene Expression ◽

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Type I ◽

Dependent Manner ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor

ABSTRACT A myriad of stimuli including proinflammatory cytokines, viruses, and chemical and mechanical insults activate a kinase complex composed of IκB kinase β (IKK-β), IKK-α, and IKK-γ/N, leading to changes in NF-κB-dependent gene expression. However, it is not clear how the NF-κB response is tailored to specific cellular insults. Signaling molecule that interacts with mouse pelle-like kinase (SIMPL) is a signaling component required for tumor necrosis factor alpha (TNF-α)-dependent but not interleukin-1-dependent NF-κB activation. Herein we demonstrate that nuclear localization of SIMPL is required for type I TNF receptor-induced NF-κB activity. SIMPL interacts with nuclear p65 in a TNF-α-dependent manner to promote endogenous NF-κB-dependent gene expression. The interaction between SIMPL and p65 enhances p65 transactivation activity. These data support a model in which TNF-α activation of NF-κB dependent-gene expression requires nuclear relocalization of p65 as well as nuclear relocalization of SIMPL, generating a TNF-α-specific induction of gene expression.

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Interleukin-2-induced Tumor Necrosis Factor-alpha (TNF-α) Gene Expression in Human Alveolar Macrophages and Blood Monocytes

American Review of Respiratory Disease ◽

10.1164/ajrccm/139.2.335 ◽

1989 ◽

Vol 139 (2) ◽

pp. 335-342 ◽

Cited By ~ 57

Author(s):

Robert M. Strieter ◽

Daniel G. Remick ◽

Joseph P. Lynch ◽

Robert N. Spengler ◽

Steven L. Kunkel

Keyword(s):

Gene Expression ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Interleukin 2 ◽

Blood Monocytes ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Human Alveolar Macrophages ◽

Factor Alpha ◽

Necrosis Factor

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

Infection and Immunity ◽

10.1128/iai.68.7.4075-4083.2000 ◽

2000 ◽

Vol 68 (7) ◽

pp. 4075-4083 ◽

Cited By ~ 104

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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E1A Sensitizes Cells to Tumor Necrosis Factor Alpha by Downregulating c-FLIPS

Journal of Virology ◽

10.1128/jvi.77.4.2651-2662.2003 ◽

2003 ◽

Vol 77 (4) ◽

pp. 2651-2662 ◽

Cited By ~ 45

Author(s):

Denise Perez ◽

Eileen White

Keyword(s):

Gene Expression ◽

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Caspase 8 ◽

Necrosis Factor Alpha ◽

Signaling Complex ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor

ABSTRACT Tumor necrosis factor alpha (TNF-α) activates both apoptosis and NF-κB-dependent survival pathways, the former of which requires inhibition of gene expression to be manifested. c-FLIP is a TNF-α-induced gene that inhibits caspase-8 activation during TNF-α signaling. Adenovirus infection and E1A expression sensitize cells to TNF-α by allowing apoptosis in the absence of inhibitors of gene expression, suggesting that it may be disabling a survival signaling pathway. E1A promoted TNF-α-mediated activation of caspase-8, suggesting that sensitivity was occurring at the level of the death-inducing signaling complex. Furthermore, E1A expression downregulated c-FLIPS expression and prevented its induction by TNF-α. c-FLIPS and viral FLIP expression rescued E1A-mediated sensitization to TNF-α by restoring the resistance of caspase-8 to activation, thereby preventing cell death. E1A inhibited TNF-α-dependent induction of c-FLIPS mRNA and stimulated ubiquitination- and proteasome-dependent degradation of c-FLIPS protein. Since elevated c-FLIP levels confer resistance to apoptosis and promote tumorigenicity, interference with its induction by NF-κB and stimulation of its destruction in the proteasome may provide novel therapeutic approaches for facilitating the elimination of apoptosis-refractory tumor cells.

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Altered levels of inhibitory cytokines in patients with thalassemia major and gingival inflammation

Brazilian Dental Science ◽

10.14295/bds.2019.v22i3.1708 ◽

2019 ◽

Vol 22 (3) ◽

pp. 349-357

Author(s):

Aliye Akcalı ◽

Selda Kahraman Çeneli ◽

Pınar Meriç ◽

Ayse Nalbantsoy ◽

Özgün Ozçaka ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Thalassemia Major ◽

Interleukin 10 ◽

Gingival Inflammation ◽

Necrosis Factor Alpha ◽

Healthy Group ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor

Objective: To evaluate local and systemic levels of interleukin-10 (IL-10), IL-33, and tumor necrosis factor alpha (TNF-α) in Thalassemia major (TM) in the presence of gingival inflammation. Material and Methods: 58 patients (TM, n=29 and systemically healthy controls, n=29) were included to the study. IL-10, IL-33, and TNF-α levels were evaluated in gingival crevicular fluid (GCF), saliva and serum. Clinical periodontal measurements were recorded. Results: GCF IL-33 total amounts in TM and gingivitis group were elevated compared to systemically and periodontally healthy group (p=0.01). GCF IL-10, IL-33 and TNF-α concentrations were higher in TM and periodontally healthy group than the systemically healthy and gingivitis group (p=0.02, p=0.008, p=0.003). Serum IL-10 levels were elevated in TM and gingivitis compared to the systemically healthy and gingivitis (p=0.0009) and systemically and periodontally healthy (p=0.0007) groups. Serum IL-10 and TNF-α levels in TM and periodontally healthy group were higher than systemically and periodontally healthy group (p=0.01 and p=0.02). Conclusion: TM may potentially alter circulating levels of IL-33 and IL-10 and therefore, may affect the degree of periodontal inflammation locally or vice versa. Yet, the underlying mechanism linking the hematologic condition is not clear and deserves further investigation. KeywordsGingivitis; Thalassemia major; Interleukin-10; Interleukin-33; Tumor Necrosis Factor-alpha.

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