scholarly journals Tula hantavirus infection of Vero E6 cells induces apoptosis involving caspase 8 activation

2004 ◽  
Vol 85 (11) ◽  
pp. 3261-3268 ◽  
Author(s):  
Xiao-Dong Li ◽  
Sami Kukkonen ◽  
Olli Vapalahti ◽  
Alexander Plyusnin ◽  
Hilkka Lankinen ◽  
...  
Keyword(s):  
Influenza A ◽  
Time Course ◽  
Caspase 3 ◽  
Hantavirus Infection ◽  
Caspase 8 ◽  
Type I ◽  
Tnf Receptor ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Hantaviruses are known to cause two severe human diseases: haemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. The mechanisms of pathogenesis of these two diseases are progressively becoming understood. Recently, two hantaviruses, Hantaan and Prospect Hill were reported to cause programmed cell death of Vero E6 cells. This study shows that Tula hantavirus (TULV) infection efficiently triggers an apoptotic programme in infected Vero E6 cells, and that the replication of TULV is required for the activation of caspase 3 and the cleavage of poly (ADP-ribose) polymerase, two molecular hallmarks of apoptosis. The enforced treatment of infected Vero E6 cells with tumour necrosis factor alpha (TNF-α), but not interferon alpha (IFN-α), advanced the time course of apoptosis. Furthermore, caspase 8 was activated on day 4 post-infection, the same day when caspase 3 was activated. TNF receptor 1 was induced during a late stage of TULV infection. These data suggest that, unlike during influenza A virus infection, TNF-α, but not type I IFN-α/β, may contribute significantly to apoptosis in a synergistic manner with TULV propagation. Interestingly, pretreatment with a broad-spectrum caspase inhibitor, z-VAD-fmk, efficiently inhibited apoptosis of TULV-infected Vero E6 cells. Taken together, these results suggest that TULV replication initiates a typical apoptotic programme involving caspase 8 activation.

scholarly journals Tumor Necrosis Factor Alpha Enhances Actinobacillus actinomycetemcomitans Leukotoxin-Induced HL-60 Cell Apoptosis by Stimulating Lymphocyte Function-Associated Antigen 1 Expression†

2004 ◽  
Vol 72 (1) ◽  
pp. 269-276 ◽  
Author(s):  
Noboru Yamaguchi ◽  
Chie Kubo ◽  
Yoshikazu Masuhiro ◽  
Edward T. Lally ◽  
Toshihiko Koga ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Tumor Necrosis ◽  
Caspase 3 ◽  
Actinobacillus Actinomycetemcomitans ◽  
Lymphocyte Function ◽  
Tnf Receptor ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT We demonstrated previously that Actinobacillus actinomycetemcomitans leukotoxin (Ltx) is greatly able to induce apoptotic signaling in cells that are positive for lymphocyte function-associated antigen 1 (LFA-1), a cell receptor of Ltx. We investigated in this study whether inflammatory cytokines can regulate apoptosis of human leukemic HL-60 cells induced by Ltx. Of the cytokines tested, tumor necrosis factor alpha (TNF-α) significantly enhanced the Ltx-induced cell apoptosis. Northern and Western blotting analyses showed that TNF-α enhanced the expression of CD11a in the cells at both the mRNA and protein levels but did not do so for CD18 expression. TNF-α also enhanced the binding of Ltx to the cells. We also observed by measuring the mitochondrial transmembrane potential and the generation of superoxide anion that the cytokine enhanced Ltx-induced apoptosis in HL-60 cells. In addition, interleukin-1β significantly enhanced Ltx-induced cell apoptosis, although the enhancing activity was lower than that of TNF-α. These stimulatory effects of both cytokines were also observed for human polymorphonuclear leukocytes. The ability of TNF-α to increase cell susceptibility to Ltx could be inhibited by preincubation of the cells with a monoclonal antibody against TNF receptor 1 but not by preincubation of the cells with a monoclonal antibody against anti-TNF receptor 2. Furthermore, the results of an assay of caspase 3 intracellular activity (PhiPhiLuxG1D2) showed that Ltx-induced caspase 3 activation was completely neutralized by CD18 antibody treatment, although significant neutralization was also observed with anti-CD11a antibody. Taken together, the results of the present study indicate that TNF-α acts as a potent stimulator of Ltx-induced HL-60 cell apoptosis via TNF receptor 1-mediated upregulation of LFA-1 expression.

scholarly journals Tumor Necrosis Factor Alpha Inhibits Type I Collagen Synthesis through Repressive CCAAT/Enhancer-Binding Proteins

2000 ◽  
Vol 20 (3) ◽  
pp. 912-918 ◽  
Author(s):  
Patricia Greenwel ◽  
Shizuko Tanaka ◽  
Dmitri Penkov ◽  
Wen Zhang ◽  
Michelle Olive ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Type I Collagen ◽  
Type I ◽  
Necrosis Factor Alpha ◽  
Gene Coding ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Stimulation Of

ABSTRACT Extracellular matrix (ECM) formation and remodeling are critical processes for proper morphogenesis, organogenesis, and tissue repair. The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) inhibits ECM accumulation by stimulating the expression of matrix proteolytic enzymes and by downregulating the deposition of structural macromolecules such as type I collagen. Stimulation of ECM degradation has been linked to prolonged activation of jun gene expression by the cytokine. Here we demonstrate that TNF-α inhibits transcription of the gene coding for the α2 chain of type I collagen [α2(I) collagen] in cultured fibroblasts by stimulating the synthesis and binding of repressive CCAAT/enhancer proteins (C/EBPs) to a previously identified TNF-α-responsive element. This conclusion was based on the concomitant identification of C/EBPβ and C/EBPδ as TNF-α-induced factors by biochemical purification and expression library screening. It was further supported by the ability of the C/EBP-specific dominant-negative (DN) protein to block TNF-α inhibition of α2(I) collagen but not TNF-α stimulation of the MMP-13 protease. The DN protein also blocked TNF-α downregulation of the gene coding for the α1 chain of type I collagen. The study therefore implicates repressive C/EBPs in the TNF-α-induced signaling pathway that controls ECM formation and remodeling.

scholarly journals Evidence that tumor necrosis factor alpha (TNF)-induced activation of neutrophil respiratory burst on biologic surfaces is mediated by the p55 TNF receptor

Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 287-293
Author(s):  
R Menegazzi ◽  
R Cramer ◽  
P Patriarca ◽  
P Scheurich ◽  
P Dri
Keyword(s):  
Respiratory Burst ◽  
Tumor Necrosis ◽  
Tnf Receptor ◽  
Necrosis Factor Alpha ◽  
Agonistic Activity ◽  
Factor Alpha ◽  
Coated Surfaces ◽  
O2 Production ◽  
Agonistic Effect ◽  
Necrosis Factor

Polymorphonuclear leukocytes (PMN) residing on biologic surfaces respond with a vigorous respiratory burst when exposed to tumor necrosis factor alpha (TNF). PMN possess both the p55 and the p75 TNF receptors, but their role in the elicitation of the respiratory burst is not known. We addressed this problem by studying the effect of monoclonal antibodies (MoAbs) directed against the p55 TNF receptor (MoAb H398 and MoAb htr-9) and the p75 TNF receptor (MoAb utr-1) on TNF- induced production of O2- by PMN residing on fibronectin-coated surfaces. Neither the anti-p55 nor the anti-p75 MoAbs affected TNF- induced O2- production despite their known ability to competitively inhibit TNF binding to the corresponding receptor. Experiments with the antibodies alone showed that the anti-p55 MoAbs directly triggered PMN O2- production, whereas no response was elicited by the anti-p75 MoAb. PMN unresponsiveness to the anti-p75 MoAb could not be ascribed to low expression of p75 receptor, because binding of the anti-p75 MoAb utr-1 to PMN was, indeed, even higher than binding of the anti-p55 MoAb htr- 9. The agonistic activity of the anti-p55 MoAbs was comparable with that of TNF and was not or only minimally modified by the simultaneous presence of TNF. Triggering of the respiratory burst by TNF was completely prevented by Fab fragments of the anti-p55 MoAb H398. Moreover, the monovalent Fab fragments, which lacked any stimulatory effect on PMN O2- production, acquired strong agonistic activity on cross-linking with anti Fab antibodies, suggesting that the ability of the anti-p55 antibodies to stimulate PMN O2- production depends on their ability to cross-link the TNF receptors. The agonistic effect of the anti-p55 MoAbs was only observed with cells residing on fibronectin- coated surfaces and not with cells in suspension, and in terms of kinetics, dependence on beta 2 integrin-mediated adherence, microfilament integrity, and sensitivity to elevations of intracellular levels of cAMP, it was virtually indistinguishable from the agonistic effect of TNF. Taken together, these results suggest that the p55 receptor is responsible for TNF-induced triggering of the respiratory burst of PMN residing on biologic surfaces.

scholarly journals Possible Protective Effect of Diacerein on Doxorubicin-Induced Nephrotoxicity in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Marwa M. M. Refaie ◽  
Entesar F. Amin ◽  
Nashwa F. El-Tahawy ◽  
Aly M. Abdelrahman
Keyword(s):  
Protective Effect ◽  
Low Dose ◽  
Caspase 3 ◽  
Interleukin 1 ◽  
Treated Group ◽  
Limiting Factors ◽  
High Dose ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Nephrotoxicity is one of the limiting factors for using doxorubicin (DOX). Interleukin 1 has major role in DOX-induced nephrotoxicity, so we investigated the effect of interleukin 1 receptor antagonist diacerein (DIA) on DOX-induced nephrotoxicity. DIA (25 and 50 mg/kg/day) was administered orally to rats for 15 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of DOX (15 mg/kg) at the 11th day. We measured levels of serum urea, creatinine, renal reduced glutathione (GSH), malondialdehyde (MDA), total nitrites (NOx), catalase, and superoxide dismutase (SOD). In addition, caspase-3, tumor necrosis factor alpha (TNFα), nuclear factor kappa B (NFκB) expressions, and renal histopathology were assessed. Our results showed that DOX-induced nephrotoxicity was ameliorated or reduced by both doses of DIA, but diacerein high dose (DHD) showed more improvement than diacerein low dose (DLD). This protective effect was manifested by significant improvement in all measured parameters compared to DOX treated group by using DHD. DLD showed significant improvement of creatinine, MDA, NOx, GSH, histopathology, and immunohistochemical parameters compared to DOX treated group.

scholarly journals Constitutive production of interleukin-6 and tumor necrosis factor- alpha from spontaneously proliferating T cells in patients with human T- cell lymphotropic virus type-I/II

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 571-574 ◽  
Author(s):  
RB Lal ◽  
DL Rudolph
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Type I ◽  
Necrosis Factor Alpha ◽  
Human T Cell ◽  
Factor Alpha ◽  
Culture Supernatants ◽  
Necrosis Factor

Abstract The human T-cell lymphotropic viruses (HTLV) type I and type II are capable of inducing a variety of cellular genes, including many of the cytokines that regulate cell proliferation. To determine if the spontaneous proliferation of peripheral blood mononuclear cells from patients infected with HTLV-I and HTLV-II was related to coordinate expression of cytokines, we analyzed the levels of interleukin-1 beta (IL-1 beta), IL-2, IL-3, IL-4, IL-6, tumor necrosis factor-alpha (TNF- alpha) and interferon-tau (IFN-tau) in culture supernatants derived from spontaneously proliferating cells. Significantly elevated levels of IL-6 and TNF-alpha were present in culture supernatants from HTLV- I/II-infected individuals when compared with normal controls (P less than .01). Kinetic experiments showed that both IL-6 and TNF-alpha were elevated by day 5. None of the other cytokines (IL-1 beta, IL-2, IL-3, IL-4, and IFN-tau) were detectable in any of the culture. These data suggest that release of IL-6 and TNF-alpha may regulate lymphocyte proliferation in HTLV-I/II-infected individuals.

scholarly journals The MC160 Protein Expressed by the Dermatotropic Poxvirus Molluscum Contagiosum Virus Prevents Tumor Necrosis Factor Alpha-Induced NF-κB Activation via Inhibition of I Kappa Kinase Complex Formation

2006 ◽  
Vol 80 (2) ◽  
pp. 578-586 ◽  
Author(s):  
Daniel Brian Nichols ◽  
Joanna L. Shisler
Keyword(s):  
Signal Transduction ◽  
Complex Formation ◽  
Tumor Necrosis ◽  
Molluscum Contagiosum ◽  
Tnf Receptor ◽  
Molluscum Contagiosum Virus ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT The pluripotent cytokine tumor necrosis factor alpha (TNF-α) binds to its cognate TNF receptor I (TNF-RI) to stimulate inflammation via activation of the NF-κB transcription factor. To prevent the detrimental effects of TNF-α in keratinocytes infected with the molluscum contagiosum virus (MCV), this poxvirus is expected to produce proteins that block at least one step of the TNF-RI signal transduction pathway. One such product, the MC160 protein, is predicted to interfere with this cellular response because of its homology to other proteins that regulate TNF-RI-mediated signaling. We report here that expression of MC160 molecules did significantly reduce TNF-α-mediated NF-κB activation in 293T cells, as measured by gene reporter and gel mobility shift assays. Since we observed that MC160 decreased other NF-κB activation pathways, namely those activated by receptor-interacting protein, TNF receptor-associated factor 2, NF-κB-inducing kinase, or MyD88, we hypothesized that the MC160 product interfered with I kappa kinase (IKK) activation, an event common to multiple signal transduction pathways. Indeed, MC160 protein expression was associated with a reduction in in vitro IKK kinase activity and IKK subunit phosphorylation. Further, IKK1-IKK2 interactions were not detected in MC160-expressing cells, under conditions demonstrated to induce IKK complex formation, but interactions between the MC160 protein and the major IKK subunits were undetectable. Surprisingly, MC160 expression correlated with a decrease in IKK1, but not IKK2 levels, suggesting a mechanism for MC160 disruption of IKK1-IKK2 interactions. MCV has probably retained its MC160 gene to inhibit NF-κB activation by interfering with signaling via multiple biological mediators. In the context of an MCV infection in vivo, MC160 protein expression may dampen the cellular production of proinflammatory molecules and enhance persistent infections in host keratinocytes.

scholarly journals Evidence that tumor necrosis factor alpha (TNF)-induced activation of neutrophil respiratory burst on biologic surfaces is mediated by the p55 TNF receptor

Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 287-293 ◽  
Author(s):  
R Menegazzi ◽  
R Cramer ◽  
P Patriarca ◽  
P Scheurich ◽  
P Dri
Keyword(s):  
Respiratory Burst ◽  
Tumor Necrosis ◽  
Tnf Receptor ◽  
Necrosis Factor Alpha ◽  
Agonistic Activity ◽  
Factor Alpha ◽  
Coated Surfaces ◽  
O2 Production ◽  
Agonistic Effect ◽  
Necrosis Factor

Abstract Polymorphonuclear leukocytes (PMN) residing on biologic surfaces respond with a vigorous respiratory burst when exposed to tumor necrosis factor alpha (TNF). PMN possess both the p55 and the p75 TNF receptors, but their role in the elicitation of the respiratory burst is not known. We addressed this problem by studying the effect of monoclonal antibodies (MoAbs) directed against the p55 TNF receptor (MoAb H398 and MoAb htr-9) and the p75 TNF receptor (MoAb utr-1) on TNF- induced production of O2- by PMN residing on fibronectin-coated surfaces. Neither the anti-p55 nor the anti-p75 MoAbs affected TNF- induced O2- production despite their known ability to competitively inhibit TNF binding to the corresponding receptor. Experiments with the antibodies alone showed that the anti-p55 MoAbs directly triggered PMN O2- production, whereas no response was elicited by the anti-p75 MoAb. PMN unresponsiveness to the anti-p75 MoAb could not be ascribed to low expression of p75 receptor, because binding of the anti-p75 MoAb utr-1 to PMN was, indeed, even higher than binding of the anti-p55 MoAb htr- 9. The agonistic activity of the anti-p55 MoAbs was comparable with that of TNF and was not or only minimally modified by the simultaneous presence of TNF. Triggering of the respiratory burst by TNF was completely prevented by Fab fragments of the anti-p55 MoAb H398. Moreover, the monovalent Fab fragments, which lacked any stimulatory effect on PMN O2- production, acquired strong agonistic activity on cross-linking with anti Fab antibodies, suggesting that the ability of the anti-p55 antibodies to stimulate PMN O2- production depends on their ability to cross-link the TNF receptors. The agonistic effect of the anti-p55 MoAbs was only observed with cells residing on fibronectin- coated surfaces and not with cells in suspension, and in terms of kinetics, dependence on beta 2 integrin-mediated adherence, microfilament integrity, and sensitivity to elevations of intracellular levels of cAMP, it was virtually indistinguishable from the agonistic effect of TNF. Taken together, these results suggest that the p55 receptor is responsible for TNF-induced triggering of the respiratory burst of PMN residing on biologic surfaces.

scholarly journals The Mitochondrial Permeability Transition Is Required for Tumor Necrosis Factor Alpha-Mediated Apoptosis and Cytochrome c Release

1998 ◽  
Vol 18 (11) ◽  
pp. 6353-6364 ◽  
Author(s):  
Cynthia A. Bradham ◽  
Ting Qian ◽  
Konrad Streetz ◽  
Christian Trautwein ◽  
David A. Brenner ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis ◽  
Caspase 3 ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Necrosis Factor Alpha ◽  
Mitochondrial Permeability ◽  
Factor Alpha ◽  
Induced Apoptosis ◽  
Necrosis Factor

ABSTRACT This study assesses the controversial role of the mitochondrial permeability transition (MPT) in apoptosis. In primary rat hepatocytes expressing an IκB superrepressor, tumor necrosis factor alpha (TNFα) induced apoptosis as shown by nuclear morphology, DNA ladder formation, and caspase 3 activation. Confocal microscopy showed that TNFα induced onset of the MPT and mitochondrial depolarization beginning 9 h after TNFα treatment. Initially, depolarization and the MPT occurred in only a subset of mitochondria; however, by 12 h after TNFα treatment, virtually all mitochondria were affected. Cyclosporin A (CsA), an inhibitor of the MPT, blocked TNFα-mediated apoptosis and cytochrome c release. Caspase 3 activation, cytochrome c release, and apoptotic nuclear morphological changes were induced after onset of the MPT and were prevented by CsA. Depolarization and onset of the MPT were blocked in hepatocytes expressing ΔFADD, a dominant negative mutant of Fas-associated protein with death domain (FADD), or crmA, a natural serpin inhibitor of caspases. In contrast, Asp-Glu-Val-Asp-cho, an inhibitor of caspase 3, did not block depolarization or onset of the MPT induced by TNFα, although it inhibited cell death completely. In conclusion, the MPT is an essential component in the signaling pathway for TNFα-induced apoptosis in hepatocytes which is required for both cytochrome c release and cell death and functions downstream of FADD and crmA but upstream of caspase 3.

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