IL-6 PROTEIN PRODUCTION BY AIRWAY EPITHELIAL(-LIKE) CELLS DISABLED IN IL-6 mRNA DEGRADATION

Lutter, René; Loman, Stoffer; Snoek, Michiel; Roger, Thierry; Out, Theo A.; Jansen, Henk M.

doi:10.1006/cyto.1999.0728

Cited by 17 publications

(32 citation statements)

References 16 publications

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“…However, as MT did not inhibit IFN-␥-induced IL-6 production to the same extent as tryptophan, tryptophan depletion may not be the only mechanism involved. Taken together, the present findings for both NCI-H292 and Calu-3 cells provide further support for a causal relation between a reduced IL-6 and IL-8 mRNA degradation and exaggerated IL-6 and IL-8 responses by airway epithelial cells, as well as the critical role of protein synthesis in regulating these responses (17).…”

Section: Discussionsupporting

confidence: 77%

“…Previously, we have shown that NCI-H292 cells with a reduced IL-6 and IL-8 mRNA degradation show amplified IL-6 and IL-8 responses to stimuli, as reflected by steeper dose-response curves (17). Cells pre-exposed to IFN-␥ for 24 h as compared with cells not exposed to IFN-␥ showed steeper dose-response curves, particularly evident at the lower concentrations of TNF-␣ (Fig.…”

Section: Ifn-␥ Modulates Il-6 and Il-8 Responsivenessmentioning

confidence: 66%

“…Previous in vitro studies with airway epithelial-like NCI-H292 and Calu-3 cells and also primary bronchial epithelial cells indicated, however, that partial inhibition of their de novo protein synthesis resulted in exaggerated IL-6 and IL-8 responses, as reflected by steeper dose response curves and a prolonged production (17). In these epithelial cells, IL-6 and IL-8 mRNA steady state levels increased up to 100-fold, which was due predominantly to stabilization of IL-6 and IL-8 mRNA.…”

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confidence: 95%

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IFN-γ Amplifies IL-6 and IL-8 Responses by Airway Epithelial-Like Cells Via Indoleamine 2,3-Dioxygenase

Wissen

Snoek

Smids

et al. 2002

The Journal of Immunology

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Respiratory viral infections increase inflammatory responses to concurrent or secondary bacterial challenges, thereby worsening disease outcome. This potentiation of inflammation is explained at least in part by IFN-γ promoting increased sensitivity to TNF-α and LPS. We sought to determine whether and, if so, how IFN-γ can modulate proinflammatory responses to TNF-α and LPS by epithelial cells, which are key effector cells in the airways. Preincubation of airway epithelial-like NCI-H292 cells with IFN-γ resulted in a hyperresponsive IL-6 and IL-8 production to TNF-α and LPS. The underlying mechanism involved the induction of indoleamine 2,3-dioxygenase, which catabolized the essential amino acid, tryptophan. Depletion of tryptophan led to stabilization of IL-6 and IL-8 mRNA and increased IL-6 and IL-8 responses, whereas supplementing tryptophan largely restored these changes. This novel mechanism may be implicated in enhanced inflammatory responses to bacterial challenges following viral infection.

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Section: Discussionsupporting

confidence: 77%

Section: Ifn-␥ Modulates Il-6 and Il-8 Responsivenessmentioning

confidence: 66%

mentioning

confidence: 95%

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IFN-γ Amplifies IL-6 and IL-8 Responses by Airway Epithelial-Like Cells Via Indoleamine 2,3-Dioxygenase

Wissen

Snoek

Smids

et al. 2002

The Journal of Immunology

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“…The stabilization of Hsp70 mRNA was also observed with the addition of cycloheximide or puromycin, which block translation by different mecha-nisms. The stability of interleukin-6 mRNA, which is also a short half-life message, has likewise been reported to increase upon incubation with cycloheximide (Lutter et al 2000). The effect of transcriptional and translational inhibitors on Hsp70 mRNA stability may indicate that new gene expression was required for the rapid degradation of Hsp70 mRNA.…”

Section: Discussionmentioning

confidence: 99%

Heat shock protein 70 binds its own messenger ribonucleic acid as part of a gene expression self-limiting mechanism

Balakrishnan¹,

Maio²

2006

Cell Stress Chaper

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Expression of heat shock proteins is a cellular response to a variety of stressors. HSP70, the major stressinduced heat shock protein, is involved in repair and protection after the insult. However, the prolonged presence of this protein is detrimental. Consequently, Hsp70 expression must be tightly regulated. We have previously shown an increase in the degradation of Hsp70 messenger ribonucleic acid (mRNA) paralleling the accumulation of HSP70. Incubation of cells with transcriptional and translational inhibitors after heat shock resulted in a significant reduction in Hsp70 mRNA degradation. These observations suggest that newly synthesized, stress-induced factors might be involved in the decay of Hsp70 mRNA. We found that HSP70 binds directly to Hsp70 mRNA, as demonstrated by immunoprecipitation. This observation was confirmed by RNA gel-shift assays. These results are evidence for a novel and likely direct interaction between HSP70 and Hsp70 mRNA in cells after stress. This interaction may be part of a self-limiting mechanism to reduce HSP70 production, thus avoiding potential toxic effects of this protein in the absence of stress.

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“…For these studies we employed human lung-derived mucoepidermoid adenocarcinoma NCI-H292 cells, which previously were shown to facilitate replication of PIV-4 without causing marked cytopathic effects (5). Moreover, the regulation of IL-8 and IL-6 production in NCI-H292 cells has been studied in detail (24,28,29,35).…”

mentioning

confidence: 99%

Exaggerated IL-8 and IL-6 responses to TNF-α by parainfluenza virus type 4-infected NCI-H292 cells

Roger¹,

Bresser²,

Snoek³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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Respiratory viruses induce and potentiate airway inflammation, which is related to the induction of proinflammatory mediators such as interleukin (IL)-8 and IL-6. Here we report on mechanisms implicated in IL-8 and IL-6 production by airway epithelium-like NCI-H292 cells exposed to parainfluenza virus type 4a (PIV-4). PIV-4 readily infected NCI-H292 cells as reflected by intracellular PIV-4 antigen expression. PIV-4 infection triggered a biphasic IL-8 and IL-6 mRNA response. Transient transfection with truncated and mutated promoter constructs identified NF-κB and activator protein (AP)-1, and CCAAT-enhancer binding protein (C/EBP) as the relevant transcription factors for PIV-4-induced IL-8 and IL-6 gene transcription, respectively. An increase of DNA-binding activities for NF-κB and C/EBP paralleled the induction of the first and second IL-8 and IL-6 mRNA peaks, whereas the onset of AP-1 paralleled the first IL-8 mRNA peak only. The second mRNA peak, apparently dependent on viral replication, coincided also with a marked reduction of IL-8 and IL-6 mRNA degradation. Importantly, cells at the time of the reduced mRNA degradation displayed an exaggerated IL-8 and IL-6 protein production to a secondary stimulus, as exemplified by steeper dose-response curves to TNF-α. Thus PIV-4 infection enhances epithelial IL-8 and IL-6 production by transcriptional and posttranscriptional mechanisms. The previously unrecognized phase of reduced IL-8 and IL-6 mRNA degradation and the concurrent amplified epithelial IL-8 and IL-6 responses may play an important role in virus-induced potentiation of airway inflammation.

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IL-6 PROTEIN PRODUCTION BY AIRWAY EPITHELIAL(-LIKE) CELLS DISABLED IN IL-6 mRNA DEGRADATION

Cited by 17 publications

References 16 publications

IFN-γ Amplifies IL-6 and IL-8 Responses by Airway Epithelial-Like Cells Via Indoleamine 2,3-Dioxygenase

IFN-γ Amplifies IL-6 and IL-8 Responses by Airway Epithelial-Like Cells Via Indoleamine 2,3-Dioxygenase

Heat shock protein 70 binds its own messenger ribonucleic acid as part of a gene expression self-limiting mechanism

Exaggerated IL-8 and IL-6 responses to TNF-α by parainfluenza virus type 4-infected NCI-H292 cells

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