TNF-α-induced programmed cell death in the pathogenesis of acquired aplastic anemia

2015 ◽  
Vol 8 (4) ◽  
pp. 515-526 ◽  
Author(s):  
Yongfeng Chen ◽  
Zhenyou Zou ◽  
Zhongmin Wu ◽  
Zhiqiang Zhao ◽  
Xinjing Luo ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Aplastic Anemia ◽  
Tnf Α

scholarly journals Yersinia enterocolitica Impairs Activation of Transcription Factor NF-κB: Involvement in the Induction of Programmed Cell Death and in the Suppression of the Macrophage Tumor Necrosis Factor α Production

1998 ◽  
Vol 187 (7) ◽  
pp. 1069-1079 ◽  
Author(s):  
Klaus Ruckdeschel ◽  
Suzanne Harb ◽  
Andreas Roggenkamp ◽  
Mathias Hornef ◽  
Robert Zumbihl ◽  
...  
Keyword(s):  
Cell Death ◽  
Transcription Factor ◽  
Tumor Necrosis Factor ◽  
Programmed Cell Death ◽  
Proteasome Inhibitor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

In this study, we investigated the activity of transcription factor NF-κB in macrophages infected with Yersinia enterocolitica. Although triggering initially a weak NF-κB signal, Y. enterocolitica inhibited NF-κB activation in murine J774A.1 and peritoneal macrophages within 60 to 90 min. Simultaneously, Y. enterocolitica prevented prolonged degradation of the inhibitory proteins IκB-α and IκB-β observed by treatment with lipopolysaccharide (LPS) or nonvirulent, plasmid-cured yersiniae. Analysis of different Y. enterocolitica mutants revealed a striking correlation between the abilities of these strains to inhibit NF-κB and to suppress the tumor necrosis factor α (TNF-α) production as well as to trigger macrophage apoptosis. When NF-κB activation was prevented by the proteasome inhibitor MG-132, nonvirulent yersiniae as well as LPS became able to trigger J774A.1 cell apoptosis and inhibition of the TNF-α secretion. Y. enterocolitica also impaired the activity of NF-κB in epithelial HeLa cells. Although neither Y. enterocolitica nor TNF-α could induce HeLa cell apoptosis alone, TNF-α provoked apoptosis when activation of NF-κB was inhibited by Yersinia infection or by the proteasome inhibitor MG-132. Together, these data demonstrate that Y. enterocolitica suppresses cellular activation of NF-κB, which inhibits TNF-α release and triggers apoptosis in macrophages. Our results also suggest that Yersinia infection confers susceptibility to programmed cell death to other cell types, provided that the appropriate death signal is delivered.

scholarly journals Flagellin/TLR5 responses in epithelia reveal intertwined activation of inflammatory and apoptotic pathways

2006 ◽  
Vol 290 (1) ◽  
pp. G96-G108 ◽  
Author(s):  
Hui Zeng ◽  
Huixia Wu ◽  
Valerie Sloane ◽  
Rheinallt Jones ◽  
Yimin Yu ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Programmed Cell Death ◽  
Pathogenic Bacteria ◽  
Caspase Activation ◽  
Extrinsic Pathway ◽  
Tnf Α ◽  
Proinflammatory Responses ◽  
Apoptotic Pathways ◽  
Toll Like Receptor 5

Flagellin, the primary structural component of bacterial flagella, is recognized by Toll-like receptor 5 (TLR5) present on the basolateral surface of intestinal epithelial cells. Utilizing biochemical assays of proinflammatory signaling pathways and mRNA expression profiling, we found that purified flagellin could recapitulate the human epithelial cell proinflammatory responses activated by flagellated pathogenic bacteria. Flagellin-induced proinflammatory activation showed similar kinetics and gene specificity as that induced by the classical endogenous proinflammatory cytokine TNF-α, although both responses were more rapid than that elicited by viable flagellated bacteria. Flagellin, like TNF-α, activated a number of antiapoptotic mediators, and pretreatment of epithelial cells with this bacterial protein could protect cells from subsequent bacterially mediated apoptotic challenge. However, when NF-κB-mediated or phosphatidylinositol 3-kinase/Akt proinflammatory signaling was blocked, flagellin could induce programmed cell death. Consistently, we demonstrate that flagellin and viable flagellate Salmonella induces both the extrinsic and intrinsic caspase activation pathways, with the extrinsic pathway (caspase 8) activated by purified flagellin in a TLR5-dependant fashion. We conclude that interaction of flagellin with epithelial cells induces caspase activation in parallel with proinflammatory responses. Such intertwining of proinflammatory and apoptotic signaling mediated by bacterial products suggests roles for host programmed cell death in the pathogenesis of enteric infections.

PD-L1 and PD-1 expressed in trigeminal ganglia may inhibit pain in an acute migraine model

Cephalalgia ◽  
2019 ◽  
Vol 40 (3) ◽  
pp. 288-298
Author(s):  
Suming Shi ◽  
Yuhang Han ◽  
Dan Wang ◽  
Ping Guo ◽  
Jiali Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Calcitonin Gene Related Peptide ◽  
Trigeminal Ganglia ◽  
Acute Migraine ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Tnf Α ◽  
Immunofluorescence Labeling

Background Neurogenic inflammation, mediated by the activation of primary neurons, is thought to be an important factor in migraine pathophysiology. Programmed cell death ligand-1 (PD-L1) can suppress the immune response through the Programmed cell death-1 receptor. However, the role of PD-L1/PD-1 in migraine remains unclear. In this study we evaluated the expression and role of PD-L1/PD-1 in the trigeminal ganglia in an animal model of acute migraine. Methods Acute nitroglycerin induces acute mechanical hyperalgesia that can be used as a readout of migraine-like pain. We investigated the expression of PD-L1 and PD-1 in the trigeminal ganglia in a mouse model by means of immunofluorescence labeling, quantitative reverse transcription-polymerase chain reaction and western blotting. We explored the effects of PD-1 in a migraine model by the von Frey test and by analyzing the expression of calcitonin gene-related peptide, interleukin-1β (IL-1β), interleukin-18 (IL-18), Tumor Necrosis Factor-α (TNF-α), interleukin-6 (IL-6) and transient receptor potential vanilloid (TRPV4) after the intravenous injection of a PD-1 inhibitor. Results PD-L1 and PD-1 immunoreactivity were present in healthy trigeminal ganglia neurons. The mRNA levels of PD-L1 and PD-1 were significantly elevated 2 h, 4 h and 6 h after acute nitroglycerin treatment ( p < 0.05). The protein levels of PD-L1 were significantly increased 2 h, 4 h and 6 h after treatment, and PD-1 was significantly increased at 2 h and 6 h. The blockade of PD-1 increased acute nitroglycerin-induced hyperalgesia, and this effect was accompanied by a more significant increase in calcitonin gene-related peptide, IL-1β, TNF-α, IL-6 and IL-18 in the trigeminal ganglia. Conclusion These findings suggest that PD-L1 and PD-1 might inhibit migraine-like pain by downregulating CGRP and inflammatory factors in the trigeminal ganglia. The use of PD-L1 and PD-1 as analgesics should be further studied.

Exacerbated tissue destruction in DSS-induced acute colitis of OPN-null mice is associated with downregulation of TNF-α expression and non-programmed cell death

2006 ◽  
Vol 208 (3) ◽  
pp. 629-639 ◽  
Author(s):  
Andre Paes Batista da Silva ◽  
Aaron Pollett ◽  
Susan R. Rittling ◽  
David T. Denhardt ◽  
Jaro Sodek ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Tissue Destruction ◽  
Acute Colitis ◽  
Tnf Α

scholarly journals Peripheral Blood Mononuclear Cells Induce Programmed Cell Death in Human Endothelial Cells and May Prevent Repair: Role of Cytokines

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 1931-1938 ◽  
Author(s):  
Heidrun Lindner ◽  
Ernst Holler ◽  
Birgit Ertl ◽  
Gabriele Multhoff ◽  
Manuela Schreglmann ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Blood Mononuclear Cells

Abstract Human umbilical vein endothelial cells (HUVECs) undergo programmed cell death (apoptosis) after coculture with peripheral blood mononuclear cells (PBMCs) preactivated by ionizing radiation (IR) or by bacterial endotoxin (lipopolysaccharide [LPS]). Cell-to-cell contact-mediated apoptosis could be blocked in both cases by anti–tumor necrosis factor-α (anti–TNF-α) monoclonal antibody MAK195 and also by the antagonistic cytokine interleukin-10 (IL-10). Cell-free PBMC supernatants from both preactivation treatments were sufficient to trigger endothelial apoptosis. In contrast, MAK195 and IL-10 were found to be ineffective in this system, suggesting a TNF-α–independent mechanism. However, N-Acetylcystein, an antioxidant, fully abrogated programmed cell death mediated by the supernatant of IR-treated PBMCs, but not of LPS-treated PBMCs. Additionally, we found that coculture and cell-free supernatants of preactivated as well as untreated PBMCs caused cell cycle arrest in proliferating EC in G0/1 , which could be relieved by IL-10, but not by anti–TNF-α. Further analysis showed that transforming growth factor-β, which was constitutively expressed in the supernatant of PBMCs, namely lymphocytes, was responsible for this. These data suggest a pathophysiologic model in which preactivated PBMCs cause EC damage and may prevent blood vessel repair by arresting the proliferation of ECs. This could contribute to the understanding of various clinical endothelial complications that occur after irradiation as well as in cases of endotoxemia or related inflammatory states.

scholarly journals Proinflammatory Caspase-2-Mediated Macrophage Cell Death Induced by a Rough Attenuated Brucella suis Strain

2011 ◽  
Vol 79 (6) ◽  
pp. 2460-2469 ◽  
Author(s):  
Fang Chen ◽  
Xicheng Ding ◽  
Ying Ding ◽  
Zuoshuang Xiang ◽  
Xinna Li ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Macrophage Cell ◽  
Proinflammatory Response ◽  
Transcriptional Responses ◽  
Content Type ◽  
Caspase 1 ◽  
Pathway Gene ◽  
Tnf Α ◽  
Caspase 2

ABSTRACTBrucellaspp. are intracellular bacteria that cause an infectious disease called brucellosis in humans and many domestic and wildlife animals.B. suisprimarily infects pigs and is pathogenic to humans. The macrophage-Brucellainteraction is critical for the establishment of a chronicBrucellainfection. Our studies showed that smooth virulentB. suisstrain 1330 (S1330) prevented programmed cell death of infected macrophages and rough attenuatedB. suisstrain VTRS1 (a vaccine candidate) induced strong macrophage cell death. To further investigate the mechanism of VTRS1-induced macrophage cell death, microarrays were used to analyze temporal transcriptional responses of murine macrophage-like J774.A1 cells infected with S1330 or VTRS1. In total 17,685 probe sets were significantly regulated based on the effects of strain, time and their interactions. A miniTUBA dynamic Bayesian network analysis predicted that VTRS1-induced macrophage cell death was mediated by a proinflammatory gene (the tumor necrosis factor alpha [TNF-α] gene), an NF-κB pathway gene (the IκB-α gene), the caspase-2 gene, and several other genes. VTRS1 induced significantly higher levels of transcription of 40 proinflammatory genes than S1330. A Mann-Whitney U test confirmed the proinflammatory response in VTRS1-infected macrophages. Increased production of TNF-α and interleukin 1β (IL-1β) were also detected in the supernatants in VTRS1-infected macrophage cell culture. Hyperphosphorylation of IκB-α was observed in macrophages infected with VTRS1 but not S1330. The important roles of TNF-α and IκB-α in VTRS1-induced macrophage cell death were further confirmed by individual inhibition studies. VTRS1-induced macrophage cell death was significantly inhibited by a caspase-2 inhibitor but not a caspase-1 inhibitor. The role of caspase-2 in regulating the programmed cell death of VTRS1-infected macrophages was confirmed in another study using caspase-2-knockout mice. In summary, VTRS1 induces a proinflammatory, caspase-2- and NF-κB-mediated macrophage cell death. This unique cell death differs from apoptosis, which is not proinflammatory. It is also different from classical pyroptosis, which is caspase-1 mediated.

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