Soluble TNF-α receptors bind and neutralize over-expressed transmembrane TNF-α on macrophages, but do not inhibit its processing

Watts, Alan D.; Hunt, Nicholas H.; Madigan, Michele C.; Chaudhri, Geeta

doi:10.1002/jlb.66.6.1005

Cited by 18 publications

(16 citation statements)

References 43 publications

(59 reference statements)

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“…A corollary of these evidences is that TNF-␣ overproduction resulting from stress-induced TACE up-regulation could mediate the induction of iNOS. Indeed, BB1101, a preferred inhibitor of metalloproteinases with sheddase activity (Kupatt et al 1999;Watts et al 1999) inhibited not only stress-induced TNF-␣ release but also the expression of iNOS as demonstrated at the level of iNOS activity and protein, suggesting that TNF-␣ is involved in the expression of this NOS isoform in our model.…”

Section: Discussionmentioning

confidence: 62%

“…injected with BB1101 (a TACE inhibitor; Kupatt et al 1999;Watts et al 1999), with MK-801 ([(ϩ)-5-methyl-10,11-dihydroxy-5H-dibenzo (a,d) cyclohepten-5,10-imine]; dizocilpine), a specific non-competitive NMDA antagonist (Wong et al 1988) or with PDTC (pyrrolidine dithiocarbamate, an inhibitor of the activation of NF-B; Schreck et al 1992). Drugs were administered at the onset of the stress.…”

Section: Pharmacological Treatmentsmentioning

confidence: 99%

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The Increase in TNF-α Levels Is Implicated in NF-κB Activation and Inducible Nitric Oxide Synthase Expression in Brain Cortex after Immobilization Stress

Madrigal

Hurtado

Moro

et al. 2002

Neuropsychopharmacology

219

120

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The underlying mechanisms by which physical or psychological stress causes neurodegeneration are still unknown. We have demonstrated that the high-output and long-lasting synthesizing source of nitric oxide (NO), inducible NO synthase (iNOS), is expressed in brain cortex after three weeks of repeated stress and that its overexpression accounts for the neurodegenerative changes found in this situation. Now we have found that a short duration of stress (immobilization for 6 h) also induces the expression of iNOS in brain cortex in adult male rats. In order to elucidate the possible mechanisms involved in iNOS expression, we have studied the role of the cytokine tumor necrosis factor-␣ (TNF-␣ ) released in brain during stress. We have shown that there is an increase in soluble TNF-␣ levels after 1 h of stress in cortex and that this is preceded by an increase in TNF-␣ -convertase (TACE) activity in brain cortex as soon as 30 min after immobilization. Stress-induced increase in both TACE activity and TNF-␣ levels seems to be mediated by excitatory amino acids since they can be blocked by MK-801 (dizocilpine) (0.2 mg/kg i.p.), an antagonist of the N-methyl-D-aspartate subtype of glutamate receptor. In order to study the role of TACE and TNF-␣ in iNOS induction, a group of animals were i.p. injected with the preferred TACE inhibitor BB1101 (2 and 10 mg/kg). Indeed, BB1101 inhibited iNOS expression induced by six hours of stress. In addition, we studied the role of the transcription factor nuclear factor B (NF-B), which is Gross and Wolin 1995). In this context, we have demonstrated that restrain stress induces a generalized increase in NO production (Leza et al. 1998) and that iNOS is expressed in brain cortex of rats exposed to stress (Olivenza et al. 2000). In support of the idea that iNOS is one of the mechanisms responsible for the functional damage in this condition, we have also demonstrated that aminoguanidine, a preferred inhibitor of iNOS, protects against cell damage produced by immobilization stress in rats (Olivenza et al. 2000; Madrigal et al. 2000), an experimental procedure used as a model of stress disorders in humans (Bremner et al. 1991).These evidences indicate that stress-induced iNOS expression in brain may mediate, at least in part, the anatomical and clinical features of neurotoxic damage found in animals and humans after exposure to uncontrollable stress (Sheline et al. 1996;Sapolsky 1996;Kim and Yoon 1998). This emphasizes the interest of the study of the mechanisms of iNOS expression after stress exposure. iNOS, as an inducible protein, is mainly regulated at the transcriptional level and is expressed after exposure of cells to several noxious agents such as cytokines and/or lipopolysaccharide (rev. in Nathan and Xie 1994). Although a considerable amount of evidence has shown that physical and psychological stress elevates plasma levels of several cytokines in animals and humans (i.e. TNF-␣ , IL-6, IFN ␥ ), the physiological significance of such elevation remains to be elucidated (Yamasu et a...

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Section: Discussionmentioning

confidence: 62%

Section: Pharmacological Treatmentsmentioning

confidence: 99%

The Increase in TNF-α Levels Is Implicated in NF-κB Activation and Inducible Nitric Oxide Synthase Expression in Brain Cortex after Immobilization Stress

Madrigal

Hurtado

Moro

et al. 2002

Neuropsychopharmacology

219

120

View full text Add to dashboard Cite

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“…1b). Irrespective to the presence of functional TNF-R1 receptors on plasma membrane of COLO 205 cells [17] it was previously reported that these cells are resistant to apoptotic stimuli induced by TNF-a [7]. Therefore it is obvious that the incubation of COLO 205 cells with a physiological concentration of TNF-a (10 ng/ml) had no detectable effect on cell morphology (Fig.…”

Section: Resultsmentioning

confidence: 94%

Bisindolylmaleimide IX facilitates extrinsic and initiates intrinsic apoptosis in TNF-α-resistant human colon adenocarcinoma COLO 205 cells

et al. 2008

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Human COLO 205 colon adenocarcinoma cells are immune to extrinsic apoptosis induced by immunomodulatory cytokines. Among the antiapoptotic mechanisms responsible for the immune escape, the overexpression of the cFLIP protein seems to be critical. cFLIP appears to inhibit the TNF-alpha-induced death receptor signal. The application of the metabolic inhibitor bisindolylmaleimide IX (Bis-IX), known as a potent PKC repressor, sensitized COLO 205 cells to TNF-alpha-mediated apoptosis. The Western-blot analysis revealed that the susceptibility of human COLO 205 cells to apoptogenic stimuli resulted from time-dependent reduction in cFLIP(L) and TRADD protein levels. At the same time, the level of FADD protein was up-regulated. Additionally, the combined TNF-alpha and Bis-IX treatment caused cleavages of Bid and procaspase-9, as well as cytochrome c release. Thus, the evidence of this study indicates that Bis-IX facilitates the death receptor signal mediated by TNF-R1. Moreover, Bis-IX alone initiated intrinsic apoptosis, which could be abolished by Bcl-2 delivery. It heralds the involvement of mitochondria in caspase-8-independent intrinsic apoptosis. In turn, the treatment with bisindolylmaleimide III (Bis-III) did not assist TNF-alpha-dependent apoptosis.

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“…1). Irrespective to the presence of functional TNF-R1 receptors on plasma membrane of COLO 205 cells [21] it was previously reported that the cells are resistant to apoptotic stimuli induced by TNF-a [13]. Therefore, it is obvious why the incubation of COLO 205 cells with a physiological concentration of TNF-a [10 ng/ ml] had no detectable effect on cell morphology (Fig.…”

Section: Sodium Butyrate Potentiates Tnf-a-mediated Apoptosismentioning

confidence: 89%

“…From this point of view, sodium butyrate (NaBt) is believed to modulate the resistance of human colon adenocarcinoma COLO 205 cells to TNF-a-induced apoptosis [21,27]. Cytotoxic drugs often induce cell death via the up-regulation of death receptors [28].…”

Section: Discussionmentioning

confidence: 99%

Sodium butyrate sensitizes human colon adenocarcinoma COLO 205 cells to both intrinsic and TNF-α-dependent extrinsic apoptosis

2009

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Overexpression of cFLIP protein seems to be critical in the antiapoptotic mechanism of immune escape of human COLO 205 colon adenocarcinoma cells. Actually, cFLIP appears to inhibit the death receptor ligand-mediated cell death. Application of the metabolic inhibitor sodium butyrate (NaBt), short-chain volatile fatty acid, sensitized COLO 205 cells to TNF-alpha-mediated apoptosis. Western-blot analysis revealed that the susceptibility of human COLO 205 cells to apoptogenic stimuli resulted from time-dependent reduction in cFLIP and simultaneous up-regulation of TNF-R1 protein levels. Additionally, the combined TNF-alpha and NaBt treatment caused cleavage of Bid and caspase-9 activation, as well as cytochrome c release from mitochondria. Thus, the evidence of this study indicates that NaBt facilitates the death receptor signal evoked by TNF-alpha. Moreover, NaBt alone initiated intrinsic apoptosis, that in turn was abolished by intracellular BCL-2 delivery. It confirms the involvement of mitochondria in the proapoptotic activity of NaBt. The activation of mitochondrial pathway was substantiated by up-regulated expression of BAK with concomitant reduction of antiapoptotic BCL-x(L), XIAP and survivin proteins. These findings suggest that NaBt could represent a good candidate for the new therapeutic strategy aimed to improve chemo- and immunotherapy of colon cancer.

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Soluble TNF-α receptors bind and neutralize over-expressed transmembrane TNF-α on macrophages, but do not inhibit its processing

Cited by 18 publications

References 43 publications

The Increase in TNF-α Levels Is Implicated in NF-κB Activation and Inducible Nitric Oxide Synthase Expression in Brain Cortex after Immobilization Stress

The Increase in TNF-α Levels Is Implicated in NF-κB Activation and Inducible Nitric Oxide Synthase Expression in Brain Cortex after Immobilization Stress

Bisindolylmaleimide IX facilitates extrinsic and initiates intrinsic apoptosis in TNF-α-resistant human colon adenocarcinoma COLO 205 cells

Sodium butyrate sensitizes human colon adenocarcinoma COLO 205 cells to both intrinsic and TNF-α-dependent extrinsic apoptosis

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