scholarly journals Prolonged, granulocyte–macrophage colony-stimulating factor-dependent, neutrophil survival following rheumatoid synovial fibroblast activation by IL-17 and TNFalpha

2008 ◽  
Vol 10 (2) ◽  
pp. R47 ◽  
Author(s):  
Greg Parsonage ◽  
Andrew Filer ◽  
Magdalena Bik ◽  
Debbie Hardie ◽  
Sian Lax ◽  
...  
Keyword(s):  
Synovial Fibroblast ◽  
Colony Stimulating Factor ◽  
Fibroblast Activation ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Neutrophil Survival ◽  
Stimulating Factor ◽  
Rheumatoid Synovial Fibroblast

scholarly journals Effects of granulocyte-macrophage colony-stimulating factor and cyclic AMP interaction on human neutrophil apoptosis

1998 ◽  
Vol 7 (6) ◽  
pp. 391-396 ◽  
Author(s):  
Cosimo Tortorella ◽  
Giuseppina Piazzolla ◽  
Felice Spaccavento ◽  
Salvatore Antonaci
Keyword(s):  
Cyclic Amp ◽  
Camp Signaling ◽  
Neutrophil Apoptosis ◽  
Colony Stimulating Factor ◽  
Dibutyryl Camp ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Neutrophil Survival ◽  
Stimulating Factor

The current study was undertaken to evaluate the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and cyclic AMP (cAMP) signaling interaction on human neutrophil apoptosis, either occurring spontaneously or induced by Fas antigen activation. Results show that GM-CSF, dibutyryl cAMP (a cAMP analog) and forskolin (an adenylate cyclase activator) are all able to suppress spontaneous neutrophil cell death. Of note however, when GM-CSF is used in combination with cAMP-elevating agents, an additive effect on neutrophil survival is observed with dibutyryl cAMP only, whereas supplementation of cell cultures with GM-CSF and forskolin results in a progressive reduction of antiapoptotic effects exerted by the single compounds. Moreover, although dibutyryl cAMP and forskolin do not affect Fas-triggered apoptotic events, they are still able to modulate the GM-CSF capacity to prolong neutrophil survival following anti-Fas IgM cell challenge, with effects similar to those respectively exerted on spontaneous neutrophil apoptosis. The data indicate that GM-CSF m ay negatively modulate the cAMP-mediated antiapoptotic pathway in human neutrophils, likely via the inhibition of adenylate cyclase activity. This would prevent an abnormal neutrophil survival as a result of cAMP signaling stimulation, which provides a novel insight into the role of GM-CSF as a physiological regulator of myeloid cell turnover.

The dual effects of TNFα on neutrophil apoptosis are mediated via differential effects on expression of Mcl-1 and Bfl-1

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 878-884 ◽  
Author(s):  
Andrew Cross ◽  
Robert J. Moots ◽  
Steven W. Edwards
Keyword(s):  
Inflammatory Diseases ◽  
Neutrophil Apoptosis ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Low Concentrations ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Opposing Effects ◽  
Neutrophil Survival ◽  
Stimulating Factor

Neutrophils have a very short half-life in the circulation, undergoing rapid death by apoptosis, but a number of agents can either delay or accelerate the rate at which these cells undergo death. TNFα can exert opposing, concentration-dependent effects on neutrophils to either accelerate their apoptosis or enhance their survival. We show that TNFα greatly increases the rate of turnover of Mcl-1, an antiapoptotic protein that plays a key role in neutrophil survival. In contrast to Mcl-1 turnover in control- or granulocyte-macrophage colony-stimulating factor (GM-CSF)–treated neutrophils that occurs via the proteasome, TNFα-accelerated Mcl-1 turnover occurs via activation of caspases. Mcl-1–depleted cells thus have accelerated rates of apoptosis. While TNFα had no effect on MCL-1 transcription, it induced expression of another antiapoptotic molecule, BFL-1. Low concentrations of TNFα (≤ 1 ng/mL) stimulated BFL-1 expression, whereas higher concentrations (≥ 10 ng/mL) triggered caspase-dependent acceleration of Mcl-1 turnover. These opposing effects on 2 separate antiapoptotic systems of neutrophils explain the divergent effects of TNFα on neutrophil apoptosis and have important implications for understanding how TNFα may affect immune function in inflammatory diseases.

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