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

1989 ◽  
Vol 139 (2) ◽  
pp. 335-342 ◽  
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

scholarly journals Role for Tumor Necrosis Factor Alpha in Murine Cytomegalovirus Transcriptional Reactivation in Latently Infected Lungs

2005 ◽  
Vol 79 (1) ◽  
pp. 326-340 ◽  
Author(s):  
Christian O. Simon ◽  
Christof K. Seckert ◽  
Doris Dreis ◽  
Matthias J. Reddehase ◽  
Natascha K. A. Grzimek
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Early Gene ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Latently Infected ◽  
Factor Alpha ◽  
Transcriptional Reactivation ◽  
Necrosis Factor

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.

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

2003 ◽  
Vol 23 (2) ◽  
pp. 526-533 ◽  
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.

scholarly journals 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

2013 ◽  
Vol 82 (1) ◽  
pp. 62-71 ◽  
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.

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

2004 ◽  
Vol 24 (21) ◽  
pp. 9317-9326 ◽  
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.

scholarly journals Serum Tumor Necrosis Factor-alpha and Interleukin-2 Concentrations in Newly Diagnosed ERBB2 (HER2/neu) Positive Breast Cancer Patients

2009 ◽  
Vol 24 (3) ◽  
pp. 142-146 ◽  
Author(s):  
Sezer Saglam ◽  
Rafi Suzme ◽  
Figen Gurdol
Keyword(s):  
Breast Cancer ◽  
Tumor Necrosis Factor ◽  
Cancer Patients ◽  
Tumor Necrosis ◽  
Interleukin 2 ◽  
Breast Cancer Patients ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Aim Cytokines have been associated with symptoms and adverse outcomes in breast cancer. Overexpression of ERBB2 (c-erb-b2; formerly HER2/neu), which is a member of the epidermal growth receptor family, is associated with involvement of lymph nodes, large tumor size, high grade, steroid receptor negativity, aneuploidy, high proliferation rate, and low overall survival in breast cancer. The aim of the study was to examine whether ERBB2 amplification has any effect on circulating levels of tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2) in breast cancer patients. Material and methods Fifty patients with primary breast carcinoma, classified as either ERBB2 (+) or (-) by the fluorescence in situ hybridization (FISH) technique, were included in the study. Cytokines were studied by ELISA according to the procedure described in the commercial kit. Results IL-2 levels were found significantly higher in ERBB2+ patients than in controls (p<0.05). A significant negative correlation existed between ERBB2 positivity and estrogen receptor status (p=0.004). Plasma TNF-α and IL-2 levels were positively correlated in ERBB2+ breast cancer patients (p<0.01). Conclusion The increase in IL-2 concentrations observed in our study suggests an activation of T cells by ERBB2 peptides.

scholarly journals Influence of Vector-Encoded Cytokines on Anti-Salmonella Immunity: Divergent Effects of Interleukin-2 and Tumor Necrosis Factor Alpha

2001 ◽  
Vol 69 (6) ◽  
pp. 3980-3988 ◽  
Author(s):  
Basel K. al-Ramadi ◽  
Mariam H. Al-Dhaheri ◽  
Nada Mustafa ◽  
Mounir AbouHaidar ◽  
Damu Xu ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 2 ◽  
Fine Tuning ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Attenuated Salmonella strains are of interest as new vaccine candidates and as vectors of cloned genes of other organisms. Attenuated strains expressing specific cytokines were constructed as a means of manipulating the immune response in various disease settings. In the present study, interleukin-2 (IL-2)-expressing (GIDIL2) or tumor necrosis factor alpha (TNF-α)-expressing (GIDTNF) strains were compared with the parent strain (BRD509) for the effect of cytokines on anti-Salmonella immunity. Expression of IL-2 resulted in a rapid clearance of the organism soon after vaccination. The reduction in GIDIL2 CFU was 50- to 300-fold higher than that of BRD509 and correlated with a markedly decreased splenomegaly. Furthermore, no evidence for any significant activation, including upregulation of surface markers and production of nitric oxide (NO), was observed in spleens of GIDIL2-injected mice. In contrast, the host response to GIDTNF was marked by an early, strong, splenic cellular influx, but surprisingly, the degree of induced splenomegaly and NO secretion was only 50% of that observed in BRD509-treated mice. Despite this, bacterial colonization of the spleen in GIDTNF-immunized animals was either slightly decreased from or equivalent to that of the BRD509-treated group, suggesting the induction of additional antimicrobial mechanisms by TNF-α. In vivo protection studies demonstrated that, at limiting doses, GIDIL2 was inferior to GIDTNF and BRD509 in its capacity to protect against virulent challenge. At high doses, however, all three strains exhibited equal protective efficacy. These results demonstrate that the immune response against intracellular bacteria can be manipulated by pathogen-expressed cytokines and open the way for further fine tuning of immune responses not only to Salmonella strains themselves but also to the heterologous gene(s) carried by them.

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

2003 ◽  
Vol 77 (4) ◽  
pp. 2651-2662 ◽  
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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