scholarly journals IL-35 and RANKL Synergistically Induce Osteoclastogenesis in RAW264 Mouse Monocytic Cells

2020 ◽  
Vol 21 (6) ◽  
pp. 2069 ◽  
Author(s):  
Yosuke Kamiya ◽  
Takeshi Kikuchi ◽  
Hisashi Goto ◽  
Iichiro Okabe ◽  
Yuhei Takayanagi ◽  
...  
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Mitogen Activated Protein Kinase ◽  
Dual Roles ◽  
Monocytic Cells ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Immunosuppressive Cytokine ◽  
Polymerase Chain ◽  
Osteoclastic Differentiation

Interleukin (IL)-35 is an immunosuppressive cytokine mainly produced by regulatory T cells. IL-35 mediates immunological functions by suppressing the inflammatory immune response. However, the role of IL-35 in bone-destructive diseases remains unclear, especially in terms of osteoclastogenesis. Therefore, the current study investigated the synergistic effect of IL-35 on osteoclastogenesis that is involved the pathogeneses of periodontitis and rheumatoid arthritis. Osteoclastic differentiation and osteoclastogenesis of RAW264 (RAW) cells induced by receptor activator of nuclear factor (NF)-κB ligand (RANKL) and IL-35 were evaluated by tartrate-resistant acid phosphate staining, hydroxyapatite resorption assays, and quantitative polymerase chain reaction. The effect of IL-35 on RANKL-stimulated signaling pathways was assessed by Western blot analysis. Costimulation of RAW cells by RANKL and IL-35 induced osteoclastogenesis significantly compared with stimulation by RANKL alone. Phosphorylations of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase tended to be increased by RANKL and IL-35 compared with RANKL or IL-35 alone. Additionally, the osteoclastogenesis induced by RANKL and IL-35 was suppressed by inhibition of ERK. In this study, IL-35 and RANKL induced osteoclastogenesis synergistically. Previous reports have shown that IL-35 suppresses the differentiation of osteoclasts. Therefore, IL-35 might play dual roles of destruction and protection in osteoclastogenesis.

miR-126 suppresses neuronal apoptosis in rats after cardiopulmonary resuscitation via regulating p38MAPK

2019 ◽  
Vol 39 (4) ◽  
pp. 563-574
Author(s):  
H Pan ◽  
M Yu ◽  
M Chen ◽  
X Wang ◽  
H Zhang ◽  
...  
Keyword(s):  
Cardiopulmonary Resuscitation ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Quantitative Polymerase Chain Reaction ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Basic Parameters ◽  
P38mapk Pathway ◽  
Polymerase Chain

In this study, we aimed to evaluate the effect of microRNA-126 (miR-126) on neuronal apoptosis in cardiopulmonary resuscitation rats and to explore the related molecular mechanism. The expression of miR-126 in brain tissues of rats after cardiopulmonary resuscitation was measured by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The basic parameters of cardiopulmonary resuscitation were recorded by miR-126 mimic injection in rats after cardiopulmonary resuscitation. Hematoxylin–eosin staining was used to observe the pathological changes of hippocampus. Immunohistochemistry was used to observe the expression of p38 and caspase-3 protein. Furthermore, the expression of p38 mitogen-activated protein kinase (p38MAPK), Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase 1/2 (ERK1/2) in rat hippocampus was detected by RT-qPCR and Western blot. In order to confirm whether miR-126 takes part in the p38MAPK pathway in the hippocampus of rats after cardiopulmonary resuscitation, the p38MAPK pathway inhibitor (SB203580) and activator (anisomycin) were added. The results showed overexpression of miR-126 could significantly increase the neurological function score and improve the pathological morphology of hippocampus in rats after cardiopulmonary resuscitation. miR-126 overexpression also could reduce the neuronal apoptosis, p38, and caspase-3 expression in the hippocampus. Moreover, the p38MAPK and JNK expression was downregulated and ERK1/2 expression was upregulated after miR-126 mimic injection ( p < 0.05). The results of inhibition of p38MAPK pathway were consistent with those of overexpression of miR-126 ( p > 0.05). This study indicated miR-126 could significantly reduce neuronal apoptosis of hippocampus in rats after cardiopulmonary resuscitation, which might be involved in the regulation of p38MAPK pathway.

ERK5 and its role in tumour development

2012 ◽  
Vol 40 (1) ◽  
pp. 251-256 ◽  
Author(s):  
Pamela A. Lochhead ◽  
Rebecca Gilley ◽  
Simon J. Cook
Keyword(s):  
Mitogen Activated Protein Kinase ◽  
Invasion And Migration ◽  
Extracellular Signal Regulated Kinase ◽  
Protein Levels ◽  
Extracellular Signal ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Tumour Cell Invasion ◽  
And Migration

The MEK5 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 5]/ERK5 pathway is the least well studied MAPK signalling module. It has been proposed to play a role in the pathology of cancer. In the present paper, we review the role of the MEK5/ERK5 pathway using the ‘hallmarks of cancer’ as a framework and consider how this pathway is deregulated. As well as playing a key role in endothelial cell survival and tubular morphogenesis during tumour neovascularization, ERK5 is also emerging as a regulator of tumour cell invasion and migration. Several oncogenes can stimulate ERK5 activity, and protein levels are increased by a novel amplification at chromosome locus 17p11 and by down-regulation of the microRNAs miR-143 and miR-145. Together, these finding underscore the case for further investigation into understanding the role of ERK5 in cancer.

scholarly journals Impact of ERK5 on the Hallmarks of Cancer

2019 ◽  
Vol 20 (6) ◽  
pp. 1426 ◽  
Author(s):  
Barbara Stecca ◽  
Elisabetta Rovida
Keyword(s):  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Biological Features ◽  
Promising Strategy ◽  
Biological Responses ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Relevant Role ◽  
Almost All

Extracellular signal-regulated kinase 5 (ERK5) belongs to the mitogen-activated protein kinase (MAPK) family that consists of highly conserved enzymes expressed in all eukaryotic cells and elicits several biological responses, including cell survival, proliferation, migration, and differentiation. In recent years, accumulating lines of evidence point to a relevant role of ERK5 in the onset and progression of several types of cancer. In particular, it has been reported that ERK5 is a key signaling molecule involved in almost all the biological features of cancer cells so that its targeting is emerging as a promising strategy to suppress tumor growth and spreading. Based on that, in this review, we pinpoint the hallmark-specific role of ERK5 in cancer in order to identify biological features that will potentially benefit from ERK5 targeting.

scholarly journals Activation of Extracellular Signal-Related Protein Kinases 1 and 2 of the Mitogen-Activated Protein Kinase Family by Lipopolysaccharide Requires Plasma in Neutrophils from Adults and Newborns

2001 ◽  
Vol 69 (5) ◽  
pp. 3143-3149 ◽  
Author(s):  
S. Bonner ◽  
S. R. Yan ◽  
D. M. Byers ◽  
R. Bortolussi
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Oxidative Burst ◽  
Mitogen Activated Protein Kinase ◽  
Related Protein ◽  
Extracellular Signal ◽  
Oxidative Response ◽  
Mitogen Activated Protein ◽  
Mediated Priming

ABSTRACT Neutrophils exposed to low concentrations of gram-negative lipopolysaccharide (LPS) become primed and have an increased oxidative response to a second stimulus (e.g., formyl-methionyl-leucyl-phenylalanine [fMLP]). In studies aimed at understanding newborn sepsis, we have shown that neutrophils of newborns are not primed in response to LPS. To further understand the processes involved in LPS-mediated priming of neutrophils, we explored the role of extracellular signal-related protein kinases (ERK 1 and 2) of the mitogen-activated protein kinase family. We found that LPS activated ERK 1 and 2 in cells of both adults and newborns and that activation was plasma dependent (maximal at ≥5%) through LPS-binding protein. Although fibronectin in plasma is required for LPS-mediated priming of neutrophils of adults assessed by fMLP-triggered oxidative burst, it was not required for LPS-mediated activation of ERK 1 and 2. LPS-mediated activation was dose and time dependent; maximal activation occurred with approximately 5 ng of LPS per ml and at 10 to 40 min. We used the inhibitor PD 98059 to study the role of ERK 1 and 2 in the LPS-primed fMLP-triggered oxidative burst. While Western blotting showed that 100 μM PD 98059 completely inhibited LPS-mediated ERK activation, oxidative response to fMLP by a chemiluminescence assay revealed that the same concentration inhibited the LPS-primed oxidative burst by only 40%. We conclude that in neutrophils, LPS-mediated activation of ERK 1 and 2 requires plasma and that this activation is not dependent on fibronectin. In addition, we found that the ERK pathway is not responsible for the lack of LPS priming in neutrophils of newborns but may be required for 40% of the LPS-primed fMLP-triggered oxidative burst in cells of adults.

scholarly journals MAPK signalling in cardiovascular health and disease: molecular mechanisms and therapeutic targets

2008 ◽  
Vol 115 (7) ◽  
pp. 203-218 ◽  
Author(s):  
Anthony J. Muslin
Keyword(s):  
Molecular Mechanisms ◽  
Cardiovascular Health ◽  
Mapk Pathway ◽  
Science Research ◽  
Pharmacological Therapy ◽  
Model Systems ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Intracellular MAPK (mitogen-activated protein kinase) signalling cascades probably play an important role in the pathogenesis of cardiac and vascular disease. A substantial amount of basic science research has defined many of the details of MAPK pathway organization and activation, but the role of individual signalling proteins in the pathogenesis of various cardiovascular diseases is still being elucidated. In the present review, the role of the MAPKs ERK (extracellular signal-regulated kinase), JNK (c-Jun N-terminal kinase) and p38 MAPK in cardiac hypertrophy, cardiac remodelling after myocardial infarction, atherosclerosis and vascular restenosis will be examined, with attention paid to genetically modified murine model systems and to the use of pharmacological inhibitors of protein kinases. Despite the complexities of this field of research, attractive targets for pharmacological therapy are emerging.

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