scholarly journals Listeria monocytogenesActivated p38 MAPK and Induced IL-8 Secretion in a Nucleotide-Binding Oligomerization Domain 1-Dependent Manner in Endothelial Cells

2005 ◽  
Vol 176 (1) ◽  
pp. 484-490 ◽  
Author(s):  
Bastian Opitz ◽  
Anja Püschel ◽  
Wiebke Beermann ◽  
Andreas C. Hocke ◽  
Stefanie Förster ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
P38 Mapk ◽  
Nucleotide Binding ◽  
Dependent Manner ◽  
Oligomerization Domain

scholarly journals Modification of the Structure of Peptidoglycan Is a Strategy To Avoid Detection by Nucleotide-Binding Oligomerization Domain Protein 1

2006 ◽  
Vol 75 (2) ◽  
pp. 706-713 ◽  
Author(s):  
Margreet A. Wolfert ◽  
Abhijit Roychowdhury ◽  
Geert-Jan Boons
Keyword(s):  
Carboxylic Acid ◽  
Glutamic Acid ◽  
Synergistic Effects ◽  
Muramyl Dipeptide ◽  
Nucleotide Binding ◽  
Diaminopimelic Acid ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Oligomerization Domain

ABSTRACT Nucleotide-binding oligomerization domain (NOD) protein 1 (NOD1) and NOD2 are pathogen recognition receptors that sense breakdown products of peptidoglycan (PGN) (muropeptides). It is shown that a number of these muropeptides can induce tumor necrosis factor alpha (TNF-α) gene expression without significant TNF-α translation. This translation block is lifted when the muropeptides are coincubated with lipopolysaccharide (LPS), thereby accounting for an apparently synergistic effect of the muropeptides with LPS on TNF-α protein production. The compounds that induced synergistic effects were also able to activate NF-κB in a NOD1- or NOD2-dependent manner, implicating these proteins in synergistic TNF-α secretion. It was found that a diaminopimelic acid (DAP)-containing muramyl tetrapeptide could activate NF-κB in a NOD1-dependent manner, demonstrating that an exposed DAP is not essential for NOD1 sensing. The activity was lost when the α-carboxylic acid of iso-glutamic acid was modified as an amide. However, agonists of NOD2, such as muramyl dipeptide and lysine-containing muramyl tripeptides, were not affected by amidation of the α-carboxylic acid of iso-glutamic acid. Many pathogens modify the α-carboxylic acid of iso-glutamic acid of PGN, and thus it appears this is a strategy to avoid recognition by the host innate immune system. This type of immune evasion is in particular relevant for NOD1.

Nucleotide-binding oligomerization domain-containing protein (NOD)-receptors 1 and 2 regulate microrna expression in endothelial cells

2018 ◽  
Vol 275 ◽  
pp. e126-e127
Author(s):  
A. Vlacil ◽  
E. Vollmeister ◽  
W. Bertrams ◽  
F. Schösser ◽  
R. Oberoi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Nucleotide Binding ◽  
Microrna Expression ◽  
Oligomerization Domain

scholarly journals Copper(II) Bis(diethyldithiocarbamate) Induces the Expression of Syndecan-4, a Transmembrane Heparan Sulfate Proteoglycan, via p38 MAPK Activation in Vascular Endothelial Cells

2018 ◽  
Vol 19 (11) ◽  
pp. 3302 ◽  
Author(s):  
Takato Hara ◽  
Hiroko Tatsuishi ◽  
Tomomi Banno ◽  
Tomoya Fujie ◽  
Chika Yamamoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Heparan Sulfate ◽  
Blood Coagulation ◽  
P38 Mapk ◽  
Vascular Endothelial Cells ◽  
Heparan Sulfate Proteoglycan ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Sulfate Proteoglycan

Proteoglycans synthesized by vascular endothelial cells are important for regulating cell function and the blood coagulation-fibrinolytic system. Since we recently reported that copper(II) bis(diethyldithiocarbamate) (Cu(edtc)2) modulates the expression of some molecules involving the antioxidant and blood coagulation systems, we hypothesized that Cu(edtc)2 may regulate the expression of proteoglycans and examined this hypothesis using a bovine aortic endothelial cell culture system. The experiments showed that Cu(edtc)2 induced the expression of syndecan-4, a transmembrane heparan sulfate proteoglycan, in a dose- and time-dependent manner. This induction required the whole structure of Cu(edtc)2—the specific combination of intramolecular copper and a diethyldithiocarbamate structure—as the ligand. Additionally, the syndecan-4 induction by Cu(edtc)2 depended on the activation of p38 mitogen-activated protein kinase (MAPK) but not the Smad2/3, NF-E2-related factor2 (Nrf2), or epidermal growth factor receptor (EGFR) pathways. p38 MAPK may be a key molecule for inducing the expression of syndecan-4 in vascular endothelial cells.

scholarly journals Nox4 NADPH oxidase-derived reactive oxygen species, via endogenous carbon monoxide, promote survival of brain endothelial cells during TNF-α-induced apoptosis

2011 ◽  
Vol 300 (2) ◽  
pp. C256-C265 ◽  
Author(s):  
Shyamali Basuroy ◽  
Dilyara Tcheranova ◽  
Sujoy Bhattacharya ◽  
Charles W. Leffler ◽  
Helena Parfenova
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Nadph Oxidase ◽  
Cell Survival ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Tnf Α ◽  
Mapk Signaling Pathways

We investigated the role of reactive oxygen species (ROS) in promoting cell survival during oxidative stress induced by the inflammatory mediator tumor necrosis factor-α (TNF-α) in cerebral microvascular endothelial cells (CMVEC) from newborn piglets. Nox4 is the major isoform of NADPH oxidase responsible for TNF-α-induced oxidative stress and apoptosis in CMVEC. We present novel data that Nox4 NADPH oxidase-derived ROS also initiate a cell survival mechanism by increasing production of a gaseous antioxidant mediator carbon monoxide (CO) by constitutive heme oxygenase-2 (HO-2). TNF-α rapidly enhanced endogenous CO production in a superoxide- and NADPH oxidase-dependent manner in CMVEC with innate, but not with small interfering RNA (siRNA)-downregulated Nox4 activity. CORM-A1, a CO-releasing compound, inhibited Nox4-mediated ROS production and enhanced cell survival in TNF-α-challenged CMVEC. The ROS-induced CO-mediated survival mechanism requires functional interactions between the protein kinase B/Akt and extracellular signal-related kinase (ERK)/p38 MAPK signaling pathways activated by TNF-α. In Akt siRNA-transfected CMVEC and in cells with pharmacologically inhibited Akt, Erk1/2, and p38 mitogen-activated protein kinase (MAPK) activities, CORM-A1 was no longer capable of blocking Nox4 activation and apoptosis caused by TNF-α. Overall, Nox4 NADPH oxidase-derived ROS initiate both death and survival pathways in TNF-α-challenged CMVEC. The ROS-dependent cell survival pathway is mediated by an endogenous antioxidant CO, which inhibits Nox4 activation via a mechanism that includes Akt, ERK1/2, and p38 MAPK signaling pathways. The ability of CO to inhibit TNF-α-induced ERK1/2 and p38 MAPK activities in an Akt-dependent manner appears to be the key element in ROS-dependent survival of endothelial cells during TNF-α-mediated brain inflammatory disease.

scholarly journals Nucleotide-Binding Oligomerization Domain Protein 2-Deficient Mice Control Infection with Mycobacterium tuberculosis

2007 ◽  
Vol 75 (11) ◽  
pp. 5127-5134 ◽  
Author(s):  
Sheetal Gandotra ◽  
Sihyug Jang ◽  
Peter J. Murray ◽  
Padmini Salgame ◽  
Sabine Ehrt
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Nucleotide Binding ◽  
Dependent Manner ◽  
Wild Type ◽  
Cytoplasmic Proteins ◽  
Antigen Presenting ◽  
Deficient Mice ◽  
Oligomerization Domain

ABSTRACT Nucleotide-binding oligomerization domain proteins (NODs) are modular cytoplasmic proteins implicated in the recognition of peptidoglycan-derived molecules. NOD2 has recently been shown to be important for host cell cytokine responses to Mycobacterium tuberculosis, to synergize with Toll-like receptor 2 (TLR2) in mediating these responses, and thus to serve as a nonredundant recognition receptor for M. tuberculosis. Here, we demonstrate that macrophages and dendritic cells from NOD2-deficient mice were impaired in the production of proinflammatory cytokines and nitric oxide following infection with live, virulent M. tuberculosis. Mycolylarabinogalactan peptidoglycan (PGN), the cell wall core of M. tuberculosis, stimulated macrophages to release tumor necrosis factor (TNF) and interleukin-12p40 in a partially NOD2-dependent manner, and M. tuberculosis PGN required NOD2 for the optimal induction of TNF. However, NOD2-deficient mice were no more susceptible to infection with virulent M. tuberculosis than wild-type mice: they controlled the replication of M. tuberculosis in lung, spleen, and liver as well as wild-type mice, and both genotypes displayed similar lung pathologies. In addition, mice doubly deficient for NOD2 and TLR2 were similarly able to control an M. tuberculosis infection. Thus, NOD2 appears to participate in the recognition of M. tuberculosis by antigen-presenting cells in vitro yet is dispensable for the control of the pathogen during in vivo infection.

Inhibitory effect of pitavastatin (NK-104) on the C-reactive-protein-induced interleukin-8 production in human aortic endothelial cells

2005 ◽  
Vol 108 (6) ◽  
pp. 515-521 ◽  
Author(s):  
Etsuko KIBAYASHI ◽  
Masaharu URAKAZE ◽  
Chikaaki KOBASHI ◽  
Mika KISHIDA ◽  
Michiyo TAKATA ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
P38 Mapk ◽  
Inflammatory Diseases ◽  
Density Lipoprotein ◽  
Interleukin 8 ◽  
Dependent Manner ◽  
C Reactive Protein ◽  
Aortic Endothelial Cells ◽  
Reactive Protein ◽  
Aortic Endothelial

Recent data have indicated that CRP (C-reactive protein) plays a role in atherosclerosis, in addition to being a marker for inflammatory diseases. IL-8 (interleukin-8), a CXC chemokine, is present in human coronary atheroma and promotes monocyte–endothelial cell adhesion. In the present study, we examined the effect of pitavastatin (NK-104), a synthetic statin (3-hydroxy-3-methylglutaryl CoA reductase inhibitor), on IL-8 production induced by CRP in human AoEC (aortic endothelial cells). We also investigated whether CRP can induce IL-8 production and if the activation of signalling pathways are functionally related. The concentrations of IL-8 in the media after stimulation with CRP were measured by ELISA, and the expression of IL-8 mRNA was assessed by Northern blot. The phosphorylation of MAPKs (mitogen-activated protein kinases) was determined by Western blot. The production of IL-8 induced by CRP (10 μg/ml) was enhanced significantly and was inhibited by pitavastatin. The expression of IL-8 mRNA was increased in a dose-dependent manner after stimulation with CRP (1–100 μg/ml), whereas expression of IL-8 mRNA induced by CRP (50 μg/ml) was significantly diminished by 5 μM pitavastatin. Furthermore, specific MAPK inhibitors (PD98059, SB203580 and SP600125) inhibited the expression of IL-8 mRNA induced by CRP (50 μg/ml). The phosphorylation of all three MAPKs [ERK (extracellular-signal-regulated kinase), p38 MAPK and JNK (c-Jun N-terminal kinase)] induced by CRP (10 μg/ml) was also significantly inhibited by pitavastatin. Our results suggest that CRP may play a role in atherosclerosis via IL-8 production and pitavastatin may prevent the progression of atherosclerosis not only by lowering plasma low-density lipoprotein cholesterol levels, but also by suppressing IL-8 production in endothelial cells through the inhibition of MAPK (ERK, p38 MAPK and JNK) pathways.

The inhibitory effect of simvastatin on the ADMA-induced inflammatory reaction is mediated by MAPK pathways in endothelial cells

2007 ◽  
Vol 85 (1) ◽  
pp. 66-77 ◽  
Author(s):  
Jun-Lin Jiang ◽  
Shan Wang ◽  
Nian-Sheng Li ◽  
Xiao-Hong Zhang ◽  
Han-Wu Deng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
P38 Mapk ◽  
Inflammatory Reaction ◽  
Nuclear Factor Κb ◽  
Intercellular Adhesion Molecule ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Intercellular Adhesion Molecule 1 ◽  
Mobility Shift ◽  
Tnf Α

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is emerging as a key contributor for endothelial dysfunction associated with inflammation. Statins can inhibit vascular inflammatory reaction and improve endothelial function. The aim of this study was to investigate in human endothelial cells the signaling pathways of ADMA-induced inflammatory reaction and potential inhibitory effects of simvastatin. Endothelial cells were cultured and used for all of the studies. Tumor necrosis factor-α (TNF-α) and soluble intercellular adhesion molecule-1 (sICAM-1) were determined by enzyme-linked immunosorbent assay. Nuclear factor-κB (NF-κB) was assayed by electrophoretic mobility shift assay. The activation of mitogen-activated protein kinases (MAPKs), including p38 MAPK and extracellular signal-related kinase (ERK1/2), were characterized by Western blot analysis. Treatment with ADMA (3–30 µmol/L) increased the concentration of sICAM-1 in a dose-dependent manner. ADMA (30 µmol/L) significantly enhanced the concentrations of TNF-α and sICAM-1, the activity of NF-κB and the phosphorylation of p38 MAPK and ERK1/2. The increased secretion of TNF-α and sICAM-1 and the increased activity of NF-κB by ADMA were altered by SB203580 (5 µmol/L) or PD98059 (20 µmol/L), but not by LY294002 (20 µmol/L). Simvastatin (0.1, 0.5, or 2.5 µmol/L) markedly inhibited the elevated concentrations of TNF-α and sICAM-1, the activity of NF-κB, and the phosphorylation of p38 MAPK and ERK1/2 induced by ADMA. Simvastatin inhibited ADMA-induced inflammatory reaction by p38 MAPK and ERK1/2 pathways in cultured endothelial cells.

scholarly journals Monomeric C-reactive protein affects cell injury and apoptosis through activation of p38 MAPK in human coronary artery endothelial cells

2020 ◽  
Author(s):  
Yong Zhang ◽  
Hongxia Cao
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
P38 Mapk ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Dependent Manner ◽  
C Reactive Protein ◽  
Human Coronary Artery ◽  
Reactive Protein ◽  
Cox 2

C-reactive protein (CRP) is an important predictor of cardiovascular events and plays a role in vascular inflammation and vessel damage. The aim of this study was to investigate the effect of pentameric CRP (pCRP) and monomeric CRP (mCRP) on the production of atherosclerosis-related factors in cultured human coronary artery endothelial cells (HCAECs). HCAECs were treated with pCRP, mCRP, p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, or transfected with p38 MAPK siRNA. Western blotting was performed to detect the expression of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-2 (ICAM-2), and vascular cell adhesion molecule 1 (VCAM-1). Proliferation, damage, and apoptosis of HCAECs were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lactate dehydrogenase (LDH), and flow cytometry, respectively. mCRP suppressed VEGF and COX-2 expression and enhanced ICAM-2 and VCAM-1 expression in HCAECs, in both dose-dependent and time-dependent manner. Except at 100 μg/ml concentration and 20-hour or 24-hour incubation, pCRP had no apparent effects. mCRP but not pCRP induced HCAEC injury and phosphorylation of p38 MAPK, and the inhibitior SB203580 reversed the effects of mCRP. mCRP promotes injury and apoptosis of HCAECs through a p38 MAPK-dependent mechanism, which provides a new therapy for the injury of HCAECs in atherosclerosis.

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