Phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase regulate induction of Mcl-1 and survival in glucocorticoid-treated human neutrophils

Saffar, Arash S.; Dragon, Stéphane; Ezzati, Peyman; Shan, Lianyu; Gounni, Abdelilah Soussi

doi:10.1016/j.jaci.2007.10.003

Cited by 45 publications

(55 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…PI3K is another key signal transducer for neutrophil survival (43,44). Induction of neutrophil survival by various antiapoptotic factors such as GM-CSF, IL-8, interferon (IFN)-β and LPS has been reported to occur through the PI3K pathway (45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

“…PI3K-mediated Akt activity can lead to prosurvival phosphorylation of Bax (48). Furthermore, glucocorticoids have been shown to inhibit neutrophil apoptosis, and this effect of glucocorticoids was found to be mediated in part by signaling through PI3K (43). PI3K activation following burn injury results in a downstream activation of nuclear factor-κB and Bad phosphorylation in neutrophils.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Interleukin-18 Delays Neutrophil Apoptosis following Alcohol Intoxication and Burn Injury

Akhtar

Kovacs

et al. 2010

Mol Med

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Interleukin-18 Delays Neutrophil Apoptosis following Alcohol Intoxication and Burn Injury

Akhtar

Kovacs

et al. 2010

Mol Med

View full text Add to dashboard Cite

“…Recent work has demonstrated that GCS are able to induce proinflammatory responses in these cells [20][21][22][23][24][25][26]. We tested the hypothesis that GCS affect TNF-a-induced synthesis and secretion of pro-and anti-inflammatory cytokines by neutrophils.…”

Section: Discussionmentioning

confidence: 99%

“…However, despite the strong capacity of GCS to inhibit inflammation, inhibition of neutrophil-driven inflammation seems to be less effective [19]. Other studies have shown that GCSs elicit proinflammatory effects on granulocytes, such as increased interleukin (IL)-1 receptor (IL-1R) type I expression on human neutrophils [20], prolonged neutrophil survival in vitro [21,22], leukocytosis in vivo [23], p38 activation in neutrophils and eosinophils [24,25], increased immunoglobulin A binding by eosinophils [25], and increased secretion of lysosomal enzymes by neutrophils [26]. Because not only proinflammatory, but also anti-inflammatory, mediators are controlled by the transcription factor NF-kB, GCSs would be expected to affect the expression of anti-inflammatory response as well, which is not often assessed.…”

mentioning

confidence: 99%

Steroids induce a disequilibrium of secreted interleukin-1 receptor antagonist and interleukin-1 synthesis by human neutrophils

Langereis

Oudijk²,

Schweizer³

et al. 2010

European Respiratory Journal

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD) is characterised by neutrophilic inflammation in the airways and these neutrophils contribute to the production of inflammatory mediators. Dampening the production of proinflammatory mediators might be an important strategy to treat COPD and glucocorticosteroids are known to do so via inhibition of nuclear factor-kB. However, this pathway is important for the control of pro-and anti-inflammatory genes.We studied the effects of dexamethasone on production and secretion of pro-inflammatory interleukin (IL)-1b and anti-inflammatory secreted IL-1 receptor antagonist (sIL-1Ra) by human neutrophils activated with tumor necrosis factor (TNF)-a.In vitro, TNF-a-stimulated neutrophils produced significant amounts of IL-1b and sIL-1Ra; this production was inhibited by dexamethasone. However, synthesis and secretion of sIL-1Ra was inhibited at lower concentrations dexamethasone compared to IL-1b, which changed the IL-1b:sIL1Ra ratio significantly. This altered ratio resulted in a more pro-inflammatory condition, as visualised by increased intercellular adhesion molecule-1 expression on human endothelial cells. In vivo, moderate-to-severe COPD patients using inhaled glucocorticosteroids have decreased plasma sILRa levels compared with mild-to-moderate patients not on glucocorticosteroid treatment.In conclusion, dexamethasone induces a pro-inflammatory shift in the IL-1b:sIL-1Ra cytokine balance in neutrophils in vitro, which might contribute to a lack of endogenous anti-inflammatory signals to dampen inflammation in vivo.

show abstract

“…Metabolism of methylprednisolone, used in many clinical trials of severe CAP, appears to be particularly responsive to the inhibitory effects of clarithromycin on CYP3A4, while metabolism of prednisone is apparently unaffected (21). Furthermore, another property of macrolides which needs to be considered in the setting of CS adjunctive therapy of CAP is the suppressive effects of these agents on neutrophils, cells which are apparently insensitive to the direct antiinflammatory actions of CS (17,22,23). Therefore, although the current literature is limited, the influence of concomitant macrolide administration, whether beneficial, detrimental or negligible, on CS metabolism, may be an issue which requires serious consideration when evaluating the outcome of most clinical trials investigating the role of adjuvant CS in severe CAP.…”

Section: Corticosteroid (Cs)/macrolide Interactionsmentioning

confidence: 99%

Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials

Feldman¹

2016

J. Thorac. Dis.

View full text Add to dashboard Cite

Improving the outcome of patients with community-acquired pneumonia (CAP) is an ongoing challenge, even in the setting of significant advances in antimicrobial chemotherapy and critical care.Recognition of the underlying involvement of inflammation-mediated organ dysfunction as a determinant of adverse outcomes in CAP has aroused intense interest in the protective potential of adjunctive antiinflammatory therapies in CAP, particularly the role of corticosteroids (CS). This is the primary topic of the current review which is focused on an evaluation of the latest meta-analyses encompassing both recent and earlier clinical trials, with particular emphasis on the stringent meta-analysis undertaken by Siemieniuk and colleagues (Ann Intern Med 2015;163:519-528). The review highlights the findings and recommendations of these and related published commentaries/critiques, while providing a brief description of those subgroups of patients who seemingly stand to benefit most from CS therapy. This is preceded by an overview of the mechanisms of the anti-inflammatory activities of CS, the interactions of these agents with macrolide antibiotics, and the potential benefits and risks of short-term administration of CS, concluding with a succinct appraisal of priority issues for ongoing and future research.

show abstract

Phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase regulate induction of Mcl-1 and survival in glucocorticoid-treated human neutrophils

Cited by 45 publications

References 49 publications

Interleukin-18 Delays Neutrophil Apoptosis following Alcohol Intoxication and Burn Injury

Interleukin-18 Delays Neutrophil Apoptosis following Alcohol Intoxication and Burn Injury

Steroids induce a disequilibrium of secreted interleukin-1 receptor antagonist and interleukin-1 synthesis by human neutrophils

Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials

Contact Info

Product

Resources

About