Tumor necrosis factor-α plus actinomycin D-induced apoptosis of L929 cells is prevented by nitric oxide

Hakoda, Shigeru; Ishikura, Hiroyasu; Takeyama, Naoshi; Tanaka, Takaya

doi:10.1007/s005950050645

Cited by 12 publications

(6 citation statements)

References 40 publications

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“…To determine whether changes in mRNA stability were also affected by MNK inhibition, we stimulated these cells with E. coli LPS for 1 h to produce a pulse of TNF mRNA and then added the transcription inhibitor actinomycin D simultaneously with either the MNK inhibitor or the DMSO control. Early time points were used to avoid apoptotic responses seen with prolonged actinomycin D stimulation (13,21). The real-time RT-PCR results (Fig.…”

Section: Resultsmentioning

confidence: 99%

MNK kinases regulate multiple TLR pathways and innate proinflammatory cytokines in macrophages

Rowlett¹,

Chrestensen²,

Nyce³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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The MNK kinases are downstream of both the p38 and ERK MAP kinase pathways and act to increase gene expression. MNK inhibition using the compound CGP57380 has recently been reported to inhibit tumor necrosis factor (TNF) production in macrophage cell lines stimulated with Escherichia coli lipopolysaccharide (LPS). However, the range of receptors that signal through the MNK kinases and the extent of the resultant cytokine response are not known. We found that TNF production was inhibited in RAW264.7 macrophage cells by CGP57380 in a dose-responsive manner with agonists for Toll-like receptor (TLR) 2 (HKLM), TLR4 (Salmonella LPS), TLR6/2 (FSL), TLR7 (imiquimod), and TLR9 (CpG DNA). CGP57380 also inhibited the peak of TNF mRNA production and increased the rate of TNF mRNA decay, effects not due to the destabilizing RNA binding protein tristetraprolin (TTP). Similar to its effects on TNF, CGP57380 caused dose-responsive inhibition of TTP production from stimulation with either LPS or CpG DNA. MNK inhibition also blocked IL-6 but permitted IL-10 production in response to LPS. Studies using bone marrow-derived macrophages (BMDM) isolated from a spontaneous mouse model of Crohn's disease-like ileitis (SAMP1/YitFc strain) revealed significant inhibition by CGP57380 of the proinflammatory cytokines TNF, IL-6, and monocyte chemoattractant protein-1 at 4 and 24 h after LPS stimulation. IL-10 production was higher in CGP53870-treated BMDM at 4 h but was similar to the controls by 24 h. Taken together, these data demonstrate that MNK kinases signal through a variety of TLR agonists and mediate a potent innate, proinflammatory cytokine response.

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Section: Resultsmentioning

confidence: 99%

MNK kinases regulate multiple TLR pathways and innate proinflammatory cytokines in macrophages

Rowlett¹,

Chrestensen²,

Nyce³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…However, the mechanistic explanations of this iNOS/NO-induced suppression of apoptosis remain hypothetical in gastric epithelial cells infected with H. pylori. Several mechanisms might contribute to the antiapoptotic effect of NO, including the suppression of the activities of multiple caspases by nitrosylation (19,21), the inhibition of Bcl-2 cleavage and cytochrome c release (18), a decrease in the formation of reactive oxygen intermediates in mitochondria (6), and the suppression of proapoptotic genes (43). We have not yet evaluated these possibilities in gastric epithelial cells infected with H. pylori.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pyloriinfection activates NF-κB signaling pathway to induce iNOS and protect human gastric epithelial cells from apoptosis

Kim

Kim²,

Jung

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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Helicobacter pylori infection induces apoptosis and inducible nitric oxide synthase (iNOS) expression in gastric epithelial cells. In this study, we investigated the effects of NF-kappaB activation and iNOS expression on apoptosis in H. pylori-infected gastric epithelial cells. The suppression of NF-kappaB significantly increased caspase-3 activity and apoptosis in H. pylori-infected MKN-45 and Hs746T gastric epithelial cell lines as well as primary gastric epithelial cells. An NF-kappaB signaling pathway via NF-kappaB-inducing kinase and IkappaB kinase-beta activation was found to be involved in the inhibition of apoptosis in H. pylori-infected gastric epithelial cells. In gastric epithelial cells transfected with retrovirus containing IkappaBalpha superrepressor, iNOS mRNA and protein levels were reduced, indicating that H. pylori infection induced the expression of iNOS by activating NF-kappaB. Moreover, a NO donor, S-nitroso-N-acetylpenicillamine (100 microM), decreased caspase-3 activity and apoptosis in NF-kappaB-suppressed cells infected with H. pylori. These results suggest that NF-kappaB activation may play a role in protecting gastric epithelial cells from H. pylori-induced apoptosis by upregulating endogenous iNOS.

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“…These two phenomena, the increase of ROS level and DNA damage, can be found either independent or one being caused by the other one. Actinomycin D (Dactinomycin, actD) causes breaks in both ds and ssDNA, and cells treated by actinomycin D are reported to be more sensitive to subsequent treatment (TRAIL, TNF-alpha) because of elevating reactive oxygen species concentration [18, 19]. DNA-damage caused by high-concentration of 5-aza-2′deoxycytidine (decitabine, DAC) was reported to be accompanied by caspase-independent ROS generation in myeloma cells [20] as well as by ROS production-dependent apoptosis in p53-mutant leukemic T-cells [21].…”

Section: Introductionmentioning

confidence: 99%

Generation of Reactive Oxygen Species during Apoptosis Induced by DNA-Damaging Agents and/or Histone Deacetylase Inhibitors

Brodská

Holoubek

2011

Oxidative Medicine and Cellular Longevity

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Reactive oxygen species play an important role in the process of apoptosis in many cell types. In this paper, we analyzed the role of ROS in DNA-damaging agents (actinomycin D or decitabine), which induced apoptosis of leukemia cell line CML-T1 and normal peripheral blood lymphocytes (PBL). The possibility of synergism with histone deacetylase inhibitors butyrate or SAHA is also reported. We found that in cancer cell line, ROS production significantly contributed to apoptosis triggering, while in normal lymphocytes treated by cytostatic or cytotoxic drugs, necrosis as well as apoptosis occurred and large heterogeneity of ROS production was measured. Combined treatment with histone deacetylase inhibitor did not potentiate actinomycin D action, whereas combination of decitabine and SAHA brought synergistic ROS generation and apoptotic features in CML cell line. Appropriate decrease of cell viability indicated promising therapeutic potential of this combination in CML, but side effects on normal PBL should be taken into attention.

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Tumor necrosis factor-α plus actinomycin D-induced apoptosis of L929 cells is prevented by nitric oxide

Cited by 12 publications

References 40 publications

MNK kinases regulate multiple TLR pathways and innate proinflammatory cytokines in macrophages

MNK kinases regulate multiple TLR pathways and innate proinflammatory cytokines in macrophages

Helicobacter pyloriinfection activates NF-κB signaling pathway to induce iNOS and protect human gastric epithelial cells from apoptosis

Generation of Reactive Oxygen Species during Apoptosis Induced by DNA-Damaging Agents and/or Histone Deacetylase Inhibitors

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