Abrogation of NF-κB signaling in human neutrophils induces neutrophil survival through sustained p38-MAPK activation

2010 ◽  
Vol 88 (4) ◽  
pp. 655-664 ◽  
Author(s):  
Jeroen D. Langereis ◽  
Hanneke A. J. A. Raaijmakers ◽  
Laurien H. Ulfman ◽  
Leo Koenderman
Keyword(s):  
P38 Mapk ◽  
Human Neutrophils ◽  
Mapk Activation ◽  
Neutrophil Survival

scholarly journals cFLIP-L Inhibits p38 MAPK Activation

2003 ◽  
Vol 278 (29) ◽  
pp. 26831-26837 ◽  
Author(s):  
Annette Grambihler ◽  
Hajime Higuchi ◽  
Steven F. Bronk ◽  
Gregory J. Gores
Keyword(s):  
P38 Mapk ◽  
Mapk Activation

p38 MAPK activation restores cardioprotection to the aged heart

2006 ◽  
Vol 41 (4) ◽  
pp. 743-743
Author(s):  
J. Peart ◽  
G. Gross ◽  
J. Headrick
Keyword(s):  
P38 Mapk ◽  
Mapk Activation

scholarly journals Hemin inhibits NO production by IL-1β-stimulated human astrocytes through induction of heme oxygenase-1 and reduction of p38 MAPK activation

2010 ◽  
Vol 7 (1) ◽  
pp. 51 ◽  
Author(s):  
Wen S Sheng ◽  
Shuxian Hu ◽  
Adam R Nettles ◽  
James R Lokensgard ◽  
Gregory M Vercellotti ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
No Production ◽  
Mapk Activation ◽  
Human Astrocytes

scholarly journals ALS-linked FUS exerts a gain of toxic function involving aberrant p38 MAPK activation

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Reddy Ranjith K. Sama ◽  
Claudia Fallini ◽  
Rodolfo Gatto ◽  
Jeanne E. McKeon ◽  
Yuyu Song ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Mapk Activation

Antimycin A induced cardioprotection is dependent on pre-ischemic p38-MAPK activation but independent of MKK3

2005 ◽  
Vol 39 (4) ◽  
pp. 709-717 ◽  
Author(s):  
A KABIR ◽  
X CAO ◽  
D GOROG ◽  
M TANNO ◽  
R BASSI ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Antimycin A ◽  
Mapk Activation

Upregulated PD-L1 delays human neutrophil apoptosis and promotes lung injury in an experimental animal model of sepsis

Blood ◽  
2021 ◽  
Author(s):  
Jia-feng Wang ◽  
Yun-peng Wang ◽  
Jian Xie ◽  
Zhen-zhen Zhao ◽  
Sahil Gupta ◽  
...  
Keyword(s):  
Animal Model ◽  
Lung Injury ◽  
Cecal Ligation ◽  
Human Neutrophils ◽  
Experimental Sepsis ◽  
Akt Phosphorylation ◽  
Effect Of Pd ◽  
Knockout Animals ◽  
Neutrophil Survival

PD-L1 is a ligand for PD-1 and its expression has been shown to be upregulated in neutrophils harvested from septic patients. However, the effect of PD-L1 on neutrophil survival and sepsis-induced lung injury remains largely unknown. Here we show PD-L1 expression negatively correlates with rates of apoptosis in human neutrophils harvested from patients with sepsis. Using co-immunoprecipitation assays on control neutrophils challenged with IFN-γ and LPS, we show PD-L1 complexes with the p85 subunit of PI3-K to activate AKT-dependent survival signaling. Conditional CRE/LoxP deletion of neutrophil PD-L1 in vivo further protected against lung injury and reduced neutrophil lung infiltration in a cecal ligation and puncture (CLP) experimental sepsis animal model. Compared to wild-type animals, PD-L1-deficient animals presented lower plasma levels of plasma TNF-α and IL-6 and higher IL-10 following CLP, and reduced seven-day mortality in CLP PD-L1 knockout animals. Taken together, our data suggest that increased PD-L1 expression on human neutrophils delays cellular apoptosis by triggering PI-3K-dependent AKT phosphorylation to drive lung injury and increase mortality during clinical and experimental sepsis.

Stimulation of pro-α1(I) collagen by TGF-β1 in mesangial cells: role of the p38 MAPK pathway

2001 ◽  
Vol 280 (3) ◽  
pp. F495-F504 ◽  
Author(s):  
Beek Yoke Chin ◽  
Amir Mohsenin ◽  
Su Xia Li ◽  
Augustine M. K. Choi ◽  
Mary E. Choi
Keyword(s):  
P38 Mapk ◽  
Intracellular Signaling ◽  
Mesangial Cells ◽  
Mapk Pathway ◽  
Dominant Negative ◽  
Glomerular Mesangial Cells ◽  
Mapk Activation ◽  
Mapk Phosphorylation ◽  
Collagen Mrna

Transforming growth factor-β1(TGF-β1) is a potent inducer of extracellular matrix protein synthesis and a key mediator of renal fibrosis. However, the intracellular signaling mechanisms by which TGF-β1stimulates this process remain incompletely understood. In this report, we examined the role of a major stress-activated intracellular signaling cascade, belonging to the mitogen-activated protein kinase (MAPK) superfamily, in mediating TGF-β1 responses in rat glomerular mesangial cells, using dominant-negative inhibition of TGF-β1 signaling receptors. We first stably transfected rat glomerular mesangial cells with a kinase-deleted mutant TGF-β type II receptor (TβR-IIM) designed to inhibit TGF-β1 signaling in a dominant-negative fashion. Next, expression of TβR-IIM mRNA was confirmed by Northern analysis. Cell surface expression and ligand binding of TβR-IIM protein were demonstrated by affinity cross-linking with 125I-labeled-TGF-β1. TGF-β1 rapidly induced p38 MAPK phosphorylation in wild-type and empty vector (pcDNA3)-transfected control mesangial cells. Interestingly, transfection with dominant-negative TβR-IIM failed to block TGF-β1-induced p38 MAPK phosphorylation. Moreover, dominant-negative TβR-IIMfailed to block TGF-β1-stimulated pro-α1(I) collagen mRNA expression and cellular protein synthesis, whereas TGF-β1-induced extracellular signal-regulated kinase (ERK) 1/ERK2 activation and antiproliferative responses were blocked by TβR-IIM. In the presence of a specific inhibitor of p38 MAPK, SB-203580, TGF-β1 was unable to stimulate pro-α1(I) collagen mRNA expression in the control and TβR-IIM-transfected mesangial cells. Finally, we confirmed that both p38 MAPK activation and pro-α1(I) collagen stimulation were TGF-β1 effects that were abrogated by dominant-negative inhibition of TGF-β type I receptor. Thus we show first demonstration of p38 MAPK activation by TGF-β1 in mesangial cells, and, given the rapid kinetics, this TGF-β1 effect is likely a direct one. Furthermore, our findings suggest that the p38 MAPK pathway functions as a component in the signaling of pro-α1(I) collagen induction by TGF-β1 in mesangial cells.

Acute adenosine preconditioning is mediated by p38 MAPK activation in discrete subcellular compartments

2005 ◽  
Vol 288 (3) ◽  
pp. H1359-H1366 ◽  
Author(s):  
Cherry Ballard-Croft ◽  
Gentian Kristo ◽  
Yukihiro Yoshimura ◽  
Easton Reid ◽  
Byron J. Keith ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Adenosine Receptor ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fraction ◽  
Control Group ◽  
Mapk Activation ◽  
Subcellular Compartments ◽  
Sb 203580

Although acute adenosine preconditioning (PC) is well established, the signaling pathways mediating this cardioprotection remain unclear. Because adenosine receptor agonists activate p38 MAPK and this kinase has been implicated in ischemic and pharmacological PC, the purpose of this study was to determine the role of p38 MAPK in acute adenosine receptor PC. The role of p38 MAPK activation in discrete subcellular compartments during ischemia-reperfusion was also determined. The following groups were used in an in vivo rat ischemia-reperfusion model: 1) control (10% DMSO iv), 2) the A1/A2a adenosine receptor AMP-579 (50 μg/kg iv), 3) AMP-579 + the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 μg/kg iv), 4) AMP-579 + the p38 MAPK inhibitor SB-203580 (1 mg/kg iv), and 5) SB-203580 alone. p38 MAPK activation was measured by Western blot analysis in cytosolic, mitochondrial, membrane, and nuclear/myofilament fractions obtained from hearts at preischemic, ischemic, and reperfusion time points. A significant reduction in infarct size was observed with AMP-579 PC, an effect blocked by DPCPX or SB-203580 pretreatment. AMP-579 treatment was associated with a significant increase in p38 MAPK activation in the nuclear/myofilament fraction before ischemia, whereas no activation of this kinase occurred during ischemia or reperfusion. In contrast, p38 MAPK was activated in the mitochondrial fraction by ischemia and in the cytosolic, mitochondrial, and membrane fractions by reperfusion in the control group. SB-203580 blocked the AMP-579-induced increase in phosphorylation of the downstream p38 substrate activating transcription factor-2. These results suggest a role for p38 MAPK activation in discrete subcellular compartments in acute adenosine A1 receptor PC.

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