Granulocyte Macrophage Colony-stimulating Factor Signaling and Proteasome Inhibition Delay Neutrophil Apoptosis by Increasing the Stability of Mcl-1

Derouet, Mathieu; Thomas, Luke W.; Cross, Andrew; Moots, Robert J.; Edwards, Steven W.

doi:10.1074/jbc.m313875200

Cited by 214 publications

(230 citation statements)

References 58 publications

Supporting

Mentioning

209

Contrasting

Unclassified

Order By: Relevance

“…4A) [18]. We subsequently demonstrated that R-roscovitine augmented the decrement in levels of Mcl-1 in neutrophils at 4 h (effect also evident at 2 h; results not shown) and that it had the ability to over-ride the protective effect of LPS, TNF-a and GM-CSF on Mcl-1 (Fig.…”

Section: R-roscovitine Down-regulates Mcl-1 Even In the Presence Of Smentioning

confidence: 57%

“…It can be down-regulated at the level of transcription, translation and even degradation [17]. Mcl-1 may be degraded in the proteasome following phosphorylation and ubiquitination or may be disposed of in a caspasedependent manner [17][18][19][20]. It is also possible that a splice variant of Mcl-1 has pro-apoptotic capability, which may perhaps explain the rapid apoptosis that can accompany Mcl-1 downregulation.…”

Section: Discussionmentioning

confidence: 99%

“…It is a rapidly transcribed, shortlived protein that is subject to prompt turnover by the proteasome [17]. Mcl-1 transcription and stability can be influenced by various signalling pathways (PI3K, ERK, glycogen synthase kinase, RAF), cytokines (GM-CSF, TNF-a) and pharmacological agents (dexamethasone, sodium salicylate) [18][19][20][21]. It is this sensitivity to the cell's environment and facility for rapid up or down-regulation that place Mcl-1 in the vanguard of apoptotic decision-making.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The cyclin‐dependent kinase inhibitor R‐roscovitine down‐regulates Mcl‐1 to override pro‐inflammatory signalling and drive neutrophil apoptosis

et al. 2010

View full text Add to dashboard Cite

Successful resolution of inflammation requires inflammatory cells such as neutrophils to undergo apoptosis prior to non-inflammatory phagocytosis by professional phagocytes. Recently, cyclin-dependent kinase (CDK) inhibitors (e.g. R-roscovitine) have been shown to induce neutrophil apoptosis and enhance the resolution of inflammation. Interestingly, NF-jB and MAPK pathways and key endogenous survival proteins (typified by Mcl-1) are involved in the regulation of neutrophil apoptosis and, in cancer-cell lines, have been implicated as possible targets of CDK inhibitors. Here, we demonstrate that R-roscovitine over-rides TNF-a and LPS-induced survival (determined by morphological examination and binding of fluorescently labelled annexin-V) of isolated peripheral blood neutrophils. This effect did not appear to be mediated via effects on early markers of neutrophil activation (e.g. surface marker expression, shape change, aggregation and superoxide anion generation), by direct inhibition of NF-jB activation (assessed by cytoplasmic IjBa proteolysis and NF-jB p65 subunit translocation) and ERK activation (determined by specific ERK phosphorylation) but due to down-regulation (at protein and mRNA level) of the survival protein Mcl-1 but not the pro-apoptotic bcl-2 homologue Bim. These findings suggest that key endogenous survival proteins may be the targets of CDK inhibitors and consequently may be of critical importance in the resolution of inflammation.

show abstract

Section: R-roscovitine Down-regulates Mcl-1 Even In the Presence Of Smentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The cyclin‐dependent kinase inhibitor R‐roscovitine down‐regulates Mcl‐1 to override pro‐inflammatory signalling and drive neutrophil apoptosis

et al. 2010

View full text Add to dashboard Cite

show abstract

“…However, lymphopenia was reported in some of the clinical studies carried out to date [4, 6,7] and may be related to inhibition of intracellular signaling pathways and/or to a direct pro-apoptotic effect of bortezomib in normal and malignant lymphocytes [17, 20, 22, 26, and A.N., unpublished observations]. On the other hand, proteasome inhibitors were shown to delay neutrophil apoptosis by favoring accumulation of the anti-apoptotic factor Mcl-1 [17,27]. Thus, it is speculated that, in some context, proteasome inhibitors may even propagate inflammatory or immune responses by preventing elimination of activated effector cells.…”

Section: Introductionmentioning

confidence: 99%

Proteasome inhibitor‐induced apoptosis in human monocyte‐derived dendritic cells

et al. 2006

View full text Add to dashboard Cite

Proteasome inhibitors possess potent antitumor activity against a broad spectrum of human malignancies. However, the effects of these compounds on the immune system still have to be clearly determined. In the present study, we have investigated the effects of proteasome inhibitors on dendritic cells (DC), antigen‐presenting cells playing a key role in the initiation of immune responses. Exposure to the proteasome inhibitors bortezomib, MG132 or epoxomicin was found to promote apoptosis of human monocyte‐derived DC and to reduce the yield of viable DC when given to monocytes early during differentiation to DC. DC apoptosis via proteasome inhibition was accompanied by mitochondria disruption and subsequent activation of the caspase cascade. Up‐regulation and intracellular redistribution of Bcl‐2‐associated X protein (Bax), a pro‐apoptotic Bcl‐2 family protein, were observed in DC treated with these compounds and represent a suitable mechanism leading to activation of the intrinsic apoptotic pathway. Finally, active protein synthesis was found to represent an upstream prerequisite for DC apoptosis induced by proteasome inhibitors, since the translation inhibitor cycloheximide blocked all of the steps of the observed apoptotic response. In conclusion, induction of apoptosis in DC may represent a novel mechanism by which proteasome inhibitors affect the immune response at the antigen‐presenting cell level.

show abstract

“…[12][13][14] BAL fluids from patients with ARDS had elevated levels of granulocyte/macrophage colony-stimulating factor that inhibits neutophil apoptosis through phosphoinositide 3-kinase and ERK pathway 15,16 and stabilizes the factor Mcl-1 that is crucial for the delay of apoptosis initiated by antiapoptotic factors. 17,18 BAL fluids from patients with ARDS was also cytotoxic to lung microvascular endothelial cells due to the presence of TNF-a and angiostatin, an inhibitor of angiogenesis in vivo. 19,20 Furthermore, apoptosis signal-regulating kinase (ASK)-1 was involved in apoptosis of pulmonary vascular endothelial cells challenged with H 2 O 2 .…”

mentioning

confidence: 99%

Angiotensin II in apoptotic lung injury: potential role in meconium aspiration syndrome

Uhal

Abdul-Hafez

2008

J Perinatol

View full text Add to dashboard Cite

Meconium aspiration injures a number of cell types in the lung, most notably airway and alveolar epithelial lining cells. Recent data show that at least some of the cell death induced by meconium occurs by apoptosis, and therefore has the potential for pharmacologic inhibition through the use of apoptosis blockers or other strategies. Related work in adult animal models of lung injury has shown that apoptosis of lung epithelial cells induces a local (that is, entirely lung tissue specific) renin-angiotensin system (RAS L ). Furthermore, this inducible RAS L is required for the apoptotic response and affects other adjacent cell types through the release of angiotensin II and related peptides. This manuscript reviews the published data supporting this viewpoint as well as more recent works that suggest the involvement of a RAS L in the perinatal lung damage associated with meconium aspiration syndrome (MAS). The implications of these findings regarding their potential for the clinical management of MAS are also discussed.

show abstract

Granulocyte Macrophage Colony-stimulating Factor Signaling and Proteasome Inhibition Delay Neutrophil Apoptosis by Increasing the Stability of Mcl-1

Cited by 214 publications

References 58 publications

The cyclin‐dependent kinase inhibitor R‐roscovitine down‐regulates Mcl‐1 to override pro‐inflammatory signalling and drive neutrophil apoptosis

The cyclin‐dependent kinase inhibitor R‐roscovitine down‐regulates Mcl‐1 to override pro‐inflammatory signalling and drive neutrophil apoptosis

Proteasome inhibitor‐induced apoptosis in human monocyte‐derived dendritic cells

Angiotensin II in apoptotic lung injury: potential role in meconium aspiration syndrome

Contact Info

Product

Resources

About