Integrins and Cytokines Activate Nuclear Transcription Factor-κB in Human Neutrophils

Kettritz, Ralph; Choi, Mira; Rolle, Susanne; Wellner, Maren; Luft, Friedrich C.

doi:10.1074/jbc.m309778200

Cited by 69 publications

(74 citation statements)

References 54 publications

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“…We initially confirmed that both TNF- § [34,35] and GM-CSF [35,36] stimulate IL-8 release from human neutrophils (Fig. 4).…”

Section: The Role Of Pi3-kinase/erk1/2 In Gm-csfand Tnf-> -Stimulatedsupporting

confidence: 57%

“…Therefore, our data would suggest that the previously stated role of PI3-kinase signaling in TNF- § -stimulated NF-‹ B activation seen in 293 embryonic kidney cells [13,37], 3T3 and endothelial cells [38,39], may have been overestimated. However, a recent paper has described GM-CSF-stimulated NF-‹ B activation in adherent but not suspended neutrophils, suggesting the potential for PI3-kinase and NF-‹ B cross-talk in these cells, although this is not operational in circulating cell [35].…”

Section: Discussionmentioning

confidence: 99%

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The survival effect of TNF‐α in human neutrophils is mediated via NF‐κB‐dependent IL‐8 release

et al. 2004

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The capacity of cytokines to modulate neutrophil apoptosis is thought to be a major factor influencing the resolution of granulocytic inflammation. We have previously shown that the late survival effect of TNF‐α in human neutrophils involves activation of both NF‐κB and phosphoinositide 3‐kinase (PI3‐kinase) pathways. In this study, we address how these pathways integrate to prevent cell death. In human neutrophils, TNF‐α (200 U/ml) induced rapid IκB‐α degradation, NF‐κB activation and IL‐8 release (31.8±5.4 pg/105 cells/2 h), whereas GM‐CSF (10 ng/ml) stimulated an equivalent IL‐8 release (26.5±4.5 pg/105 cells/2 h) without enhanced IκB‐α degradation or NF‐κB activation compared to control. Importantly, inhibition of PI3‐kinase did not modify TNF‐α ‐induced IκB‐α degradation, yet fully inhibited the survival effect of both cytokines. Inhibition of IκB‐α phosphorylation, PI3‐kinase or ERK1/2 activation blocked IL‐8 release by both cytokines. Blocking IL‐8 activity by inhibiting its synthesis or by using a neutralizing antibody enhanced the early pro‐apoptotic effectof TNF‐α and inhibited its late survival effect without affecting GM‐CSF‐induced survival. These data suggest that cross‐talk between NF‐κB and PI3‐kinase pathways in TNF‐α ‐stimulated neutrophils results from NF‐κB/ERK1/2‐dependent IL‐8 production which acts in an autocrine manner to drive PI3‐kinase‐dependent survival. In contrast, GM‐CSF‐mediated survival does not involve NF‐κB activation or IL‐8 release.

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“…We initially confirmed that both TNF- § [34,35] and GM-CSF [35,36] stimulate IL-8 release from human neutrophils (Fig. 4).…”

Section: The Role Of Pi3-kinase/erk1/2 In Gm-csfand Tnf-> -Stimulatedsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

The survival effect of TNF‐α in human neutrophils is mediated via NF‐κB‐dependent IL‐8 release

et al. 2004

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“…We hypothesized that ␣ 5 ␤ 1 -integrin-mediated signaling may affect transcriptional regulation of type I collagen genes by upregulation of a transcriptional enhancer. ␣ 5 ␤ 1 -Integrin as well as other integrins have been reported to modify activity of transcription factors in certain cell types (18,19). One such transcription factor reported to play a role in regulation of type I collagen transcription in HSC is C/EBP␤.…”

Section: Discussionmentioning

confidence: 99%

Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of α₅β₁-integrin

Dodig¹,

Ogunwale²,

Dasarathy³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Hepatic stellate cells (HSC) differ in their phenotype depending on the initiation and progression of their activation. Our hypothesis was that different mechanisms govern type I collagen synthesis depending on stage of HSC activation. We investigated the role of ␣5␤1-integrin as a regulator of type I collagen gene COL1A1 expression in primary and passaged HSC cultures using transgenic mouse containing type I collagen gene COL1A1 promoter linked to the chloramphenicol acetyltransferase (CAT) reporter gene. The ␣5␤1 protein levels increased during the activation and were highest in day 6 primary cultures but decreased in passaged HSC. CAT activity, reflecting COL1A1 expression, was upregulated by ␣5␤1-integrin. Inhibition of ␣5␤1-integrin by echistatin and blocking antibody resulted in reduced transgene activity only in early primary cultures (compared with the control, 53.3 Ϯ 12% echistatin and 58.8 Ϯ 7% blocking antibody, respectively, P Ͻ 0.05). Treatment of passaged HSC with either echistatin or blocking antibody had no effect. Fibronectin, an ␣5␤1-integrin ligand, increased transgene activity in primary (210 Ϯ 33%, P Ͻ 0.05) but not in passaged HSC cultures (119 Ϯ 8%). This ␣5␤1-integrin effect appears to be at least in part mediated by CCAAT enhancer binding protein-␤ (C/EBP␤), because fibronectin increased and ␣5-gene silencing by small interfering RNA decreased C/EBP␤ levels. In addition, C/EBP␤ knockout mice showed reduced type I collagen synthesis compared with wild-type littermates. Therefore ␣5␤1-integrin is an important regulator of type I collagen production in early primary HSC cultures but appears to have no direct role once the HSC are fully activated.

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“…Nuclear extract of human neutrophils was prepared, as described previously (19). Briefly, human neutrophils (1 ϫ 10 6 cells) were incubated with sPLA 2 -IB for several times, as indicated.…”

Section: Preparation Of Nuclear Extractsmentioning

confidence: 99%

Group IB Secretory Phospholipase A2 Stimulates CXC Chemokine Ligand 8 Production via ERK and NF-κB in Human Neutrophils

Lee

Lee³

et al. 2004

The Journal of Immunology

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Although the level of group IB secretory phospholipase A2 (sPLA2-IB) has been reported to be up-regulated during inflammatory response, the role of sPLA2-IB on the regulation of inflammation and immune responses has not been fully elucidated. In this study, we found that sPLA2-IB stimulates the expression and secretion of CXCL8 without affecting other proinflammatory cytokines, such as IL-1β or TNF α in human neutrophils. The induction of CXCL8 secretion by sPLA2-IB occurs at both the transcription and translational levels and correlates with activation of NF-κB. Moreover, the NF-κB inhibitors pyrrolidinedithiocarbamate, dexamethasone, or sulfasalazine were found to prevent CXCL8 production by sPLA2-IB in human neutrophils. In addition, the signaling events induced by sPLA2-IB included activation of the MAPK ERK and an increase in intracellular Ca2+, which are both required for CXCL8 production. The exogenous addition of sPLA2-IB did not induce arachidonic acid release from human neutrophils, and the inactivation of sPLA2-IB by EGTA did not affect CXCL8 production by sPLA2-IB in human neutrophils. Taken together, we suggest that sPLA2-IB plays a role in the modulation of inflammatory and immune responses via the sPLA2 receptor, by inducing CXCL8 in human neutrophils.

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Integrins and Cytokines Activate Nuclear Transcription Factor-κB in Human Neutrophils

Cited by 69 publications

References 54 publications

The survival effect of TNF‐α in human neutrophils is mediated via NF‐κB‐dependent IL‐8 release

The survival effect of TNF‐α in human neutrophils is mediated via NF‐κB‐dependent IL‐8 release

Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of α₅β₁-integrin

Group IB Secretory Phospholipase A2 Stimulates CXC Chemokine Ligand 8 Production via ERK and NF-κB in Human Neutrophils

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Integrins and Cytokines Activate Nuclear Transcription Factor-κB in Human Neutrophils

Cited by 69 publications

References 54 publications

The survival effect of TNF‐α in human neutrophils is mediated via NF‐κB‐dependent IL‐8 release

The survival effect of TNF‐α in human neutrophils is mediated via NF‐κB‐dependent IL‐8 release

Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of α5β1-integrin

Group IB Secretory Phospholipase A2 Stimulates CXC Chemokine Ligand 8 Production via ERK and NF-κB in Human Neutrophils

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Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of α₅β₁-integrin