Endothelin-1 induces neutrophil recruitment in adaptive inflammation via TNFα and CXCL1/CXCR2 in mice

2012 ◽  
Vol 90 (2) ◽  
pp. 187-199 ◽  
Author(s):  
Ana C. Zarpelon ◽  
Larissa G. Pinto ◽  
Thiago M. Cunha ◽  
Silvio M. Vieira ◽  
Vanessa Carregaro ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Peritoneal Cavity ◽  
Neutrophil Migration ◽  
Neutrophil Recruitment ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Endothelin 1 ◽  
Cxc Chemokine ◽  
Chemokine Ligand ◽  
Factor Α

Endothelin mediates neutrophil recruitment during innate inflammation. Herein we address whether endothelin-1 (ET-1) is involved in neutrophil recruitment in adaptive inflammation in mice, and its mechanisms. Pharmacological treatments were used to determine the role of endothelin in neutrophil recruitment to the peritoneal cavity of mice challenged with antigen (ovalbumin) or ET-1. Levels of ET-1, tumour necrosis factor α (TNFα), and CXC chemokine ligand 1 (CXCL1) were determined by enzyme-linked immunosorbent assay. Neutrophil migration and flow cytometry analyses were performed 4 h after the intraperitoneal stimulus. ET-1 induced dose-dependent neutrophil recruitment to the peritoneal cavity. Treatment with the non-selective ETA/ETB receptor antagonist bosentan, and selective ETA or ETB receptor antagonists BQ-123 or BQ-788, respectively, inhibited ET-1- and ovalbumin-induced neutrophil migration to the peritoneal cavity. In agreement with the above, the antigen challenge significantly increased levels of ET-1 in peritoneal exudates. The ET-1- and ovalbumin-induced neutrophil recruitment were reduced in TNFR1 deficient mice, and by treatments targeting CXCL1 or CXC chemokine receptor 2 (CXCR2); further, treatment with bosentan, BQ-123, or BQ-788 inhibited ET-1- and antigen-induced production of TNFα and CXCL1. Furthermore, ET-1 and ovalbumin challenge induced an increase in the number of cells expressing the Gr1+ markers in the granulocyte gate, CD11c+ markers in the monocyte gate, and CD4+ and CD45+ (B220) markers in the lymphocyte gate in an ETA- and ETB-dependent manner, as determined by flow cytometry analysis, suggesting that ET-1 might be involved in the recruitment of neutrophils and other cells in adaptive inflammation. Therefore, the present study demonstrates that ET-1 is an important mediator for neutrophil recruitment in adaptive inflammation via TNFα and CXCL1/CXCR2-dependent mechanism.

P2Y6 Receptor Contributes to Neutrophil Recruitment to Inflamed Intestinal Mucosa by Increasing Cxc Chemokine Ligand 8 Expression in an AP-1-dependent Manner in Epithelial Cells

2012 ◽  
Vol 18 (8) ◽  
pp. 1456-1469 ◽  
Author(s):  
Djordje M. Grbic ◽  
Émilie Degagné ◽  
Jean-François Larrivée ◽  
Maude S. Bilodeau ◽  
Valérie Vinette ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Mucosa ◽  
Neutrophil Recruitment ◽  
Dependent Manner ◽  
Cxc Chemokine ◽  
Chemokine Ligand ◽  
P2y6 Receptor

scholarly journals Blocking of checkpoint receptor PD-L1 aggravates osteoarthritis in macrophage-dependent manner in the mice model

2019 ◽  
Vol 33 ◽  
pp. 205873841882076 ◽  
Author(s):  
Shenghou Liu ◽  
Jiqiang Mi ◽  
Wenguang Liu ◽  
Shipeng Xiao ◽  
Chunzheng Gao
Keyword(s):  
Inflammatory Cytokine ◽  
Cruciate Ligament ◽  
Mrna Level ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Mice Model ◽  
Safranin O ◽  
Factor Α

As a chronic degenerative joint disease, osteoarthritis is among the most common diseases all over the world. In osteoarthritis, inflammation plays an important role in the generation of joint symptoms and the development of disease. When the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint is blocked, the antitumor immunity will be enhanced. We aim to illustrate the function of PD-L1 in osteoarthritis. Osteoarthritis in mice was induced by the injection of collagenase or anterior cruciate ligament transection (ACLT). Anti-PD-L1 was employed to block the signal of PD-L1. Knee joints histological sections were stained by Safranin-O. The level of cytokine was checked by enzyme-linked immunosorbent assay (ELISA) and mRNA level was shown by quantitative reverse transcriptase polymerase chain reaction. The blockade of PD-L1 signal up-regulated inflammatory response and promoted the development of osteoarthritis in mice. The inflammatory cytokine interleukin-6 and tumor necrosis factor-α expression were promoted by PD-L1 blocking in macrophages. Osteoarthritis was aggravated when the expression of inflammatory cytokine is elevated in macrophages. Our results indicated that the blockade of PD-L1 signal in macrophages elevates the expression of inflammatory cytokine and promotes the development of osteoarthritis in mice, which could be utilized as a potential diagnostic and therapeutic target for osteoarthritis patients.

scholarly journals Streptococcal M1 Protein Triggers Farnesyltransferase-Dependent Formation of CXC Chemokines in Alveolar Macrophages and Neutrophil Infiltration of the Lungs

2012 ◽  
Vol 80 (11) ◽  
pp. 3952-3959 ◽  
Author(s):  
Songen Zhang ◽  
Milladur Rahman ◽  
Su Zhang ◽  
Bengt Jeppsson ◽  
Heiko Herwald ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alveolar Macrophages ◽  
Neutrophil Migration ◽  
Neutrophil Recruitment ◽  
Lung Damage ◽  
Streptococcal Toxic Shock Syndrome ◽  
Edema Formation ◽  
M1 Protein ◽  
Cxc Chemokine

ABSTRACTThe M1 serotype ofStreptococcus pyogenesplays an important role in streptococcal toxic shock syndrome. Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been shown to inhibit streptococcal M1 protein-induced acute lung damage, although downstream mechanisms remain elusive. Protein isoprenylation, such as farnesylation and geranylgeranylation, has been suggested to regulate anti-inflammatory effects exerted by statins. Here, we examined the effect of a farnesyltransferase inhibitor (FTI-277) on M1 protein-triggered lung inflammation. Male C57BL/6 mice were treated with FTI-277 prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema, and CXC chemokine formation. Flow cytometry was used to determine Mac-1 expression on neutrophils. The gene expression of CXC chemokines was determined in alveolar macrophages by using quantitative reverse transcription (RT)-PCR. We found that the administration of FTI-277 markedly decreased M1 protein-induced accumulation of neutrophils, edema formation, and tissue damage in the lung. Notably, inhibition of farnesyltransferase abolished M1 protein-evoked production of CXC chemokines in the lung and gene expression of CXC chemokines in alveolar macrophages. Moreover, FTI-277 completely inhibited chemokine-induced neutrophil migrationin vitro. However, farnesyltransferase inhibition had no effect on M1 protein-induced expression of Mac-1 on neutrophils. Our findings suggest that farnesyltransferase is a potent regulator of CXC chemokine formation in alveolar macrophages and that inhibition of farnesyltransferase not only reduces neutrophil recruitment but also attenuates acute lung injury provoked by streptococcal M1 protein. We conclude that farnesyltransferase activity is a potential target in order to attenuate acute lung damage in streptococcal infections.

scholarly journals Human Peritoneal Mesothelial Cells Display Phagocytic and Antigen-Presenting Functions to Contribute to Intraperitoneal Immunity

2016 ◽  
Vol 26 (5) ◽  
pp. 833-838 ◽  
Author(s):  
Tanya J. Shaw ◽  
Xiang Y. Zhang ◽  
Zhiming Huo ◽  
David Robertson ◽  
Patricia A. Lovell ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Mhc Class Ii ◽  
Constitutive Expression ◽  
Class Ii ◽  
Mesothelial Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells ◽  
Antigen Presenting

AbstractMesothelial cells lining the peritoneal cavity are strategically positioned to respond to and counter intraperitoneal infections, cancer cells, and other challenges. We have investigated human peritoneal mesothelial cells (HPMCs) for phagocytic activity, expression of surface Major Histocompatibility Complex (MHC) class II and accessory molecules involved in antigen presentation, and the ability to present recall antigens to T cells. Phagocytosis of dextran, latex beads, andEscherichia coliwas observed by flow cytometry, and internalization was visualized using confocal and electron microscopy. Flow cytometry and/or cellular enzyme-linked immunosorbent assay showed constitutive expression of ICAM-1, LFA-3, and B7-1, but not B7-2 or MHC class II. Interferon-gamma induced MHC II and ICAM-1 expression in a dose- and time-dependent manner. Importantly, HPMCs induced autologous CD3+T-lymphocyte proliferation (3H incorporation) after pulse with recall antigen. Human peritoneal mesothelial cells equipped with phagocytic and antigen-presenting machinery are anticipated to have an integral role in intraperitoneal immune surveillance.

scholarly journals Dihydromyricetin attenuates inflammation through TLR4/NF-kappaB pathway

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 719-725 ◽  
Author(s):  
Nianshui Jing ◽  
Xinnan Li
Keyword(s):  
Primary Response ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Tnf Α ◽  
Cox 2 ◽  
Nf Kappab ◽  
Factor Α ◽  
Oxide Synthase

AbstractMicroglia plays a complex role in neuroinflammation, which has been implicated in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. This study aims to explore the effect and mechanism of Dihydromyricetin (DHM) on lipopolysaccharide (LPS)-induced inflammation in microglial BV-2 cells. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide (MTT) assay. The pro-inflammatory mediators and cytokines including interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α); inducible nitric oxide synthase (iNOS); and cyclooxygenase 2 (COX-2) were measured by enzyme-linked immunosorbent assay (ELISA) and/or quantitative real-time PCR (qRT-PCR). The expression of p-p65, p-IκBα, toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) were analyzed by western blot. The present study showed that DHM treatment alleviated LPS-induced viability reduction, suppressed the mRNA levels of IL-6, IL‐1β and TNF-α, inhibited the mRNA and protein expression of iNOS and COX-2, and attenuated the activation of NF-кB and TLR4 signaling in a concentration-dependent manner. In conclusion, DHM exerts an anti-inflammatory effect on LPS-induced BV-2 microglial cells, possibly through TRL4/NF-κB signaling pathway.

High levels of acetoacetate and glucose increase expression of cytokines in bovine hepatocytes, through activation of the NF-κB signalling pathway

2016 ◽  
Vol 83 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Yu Li ◽  
Hongyan Ding ◽  
Xichun Wang ◽  
Lei Liu ◽  
Dan Huang ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Blood Level ◽  
Quantitative Polymerase Chain Reaction ◽  
Signalling Pathway ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Pathway Activation ◽  
Tnf Α ◽  
Factor Α

Elevated levels of blood interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor–α (TNF–α) increase insulin resistance and result in inflammation. It is not clear whether elevated blood level of acetoacetate (ACAC) and decreased blood level of glucose, which are the predominant characteristics of clinical biochemistry in ketotic dairy cows, increase proinflammatory cytokines and subsequent inflammation. The objective of this study was to test the hypothesis that ACAC and glucose activate the NF-κB signalling pathway to regulate cytokines expression in bovine hepatocytes. Bovine hepatocytes were cultured with ACAC (0–4·8 mm) and glucose (0–5·55 mm) with or without NF-κB inhibitor PDTC for 24 h. The secretion and mRNA levels of cytokines were determined by enzyme-linked immunosorbent assay (ELISA) and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The NF-κB signalling pathway activation was evaluated by western blotting. Results showed that the secretion and expression of IL-1β, IL-6 and TNF-α increased in an ACAC dose-dependent manner. Additionally, there was an increase in the secretion and mRNA expression of these three cytokines in glucose treatment group, which increased significantly when the glucose concentrations exceed 3·33 mm. Furthermore, both ACAC and glucose upregulated NF-κB p65 protein expression and IκBα phosphorylation levels. However, these effects were reduced by PDTC. These results demonstrate that elevated levels of ACAC and glucose increase the synthesis and expression of proinflammatory factors by activating NF-κB signalling pathway in hepatocytes, which may contribute to inflammation injury in ketotic dairy cows.

Effect of bisphenol-A (BPA) on placental biomarkers for inflammation, neurodevelopment and oxidative stress

2019 ◽  
Vol 47 (7) ◽  
pp. 741-749 ◽  
Author(s):  
Yuko Arita ◽  
Hyeon Jeong Park ◽  
Aisling Cantillon ◽  
Darios Getahun ◽  
Ramkumar Menon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bisphenol A ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Oxidative Balance ◽  
Tnf Α ◽  
Placental Inflammation ◽  
Factor Α ◽  
Dose Dependent ◽  
And Oxidative Stress

Abstract Background Bisphenol-A (BPA) is a widespread pollutant whose effects on pregnant women are poorly understood. Therefore, we investigated the effects of BPA on basal and bacteria-stimulated production of proinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and IL-6], anti-inflammatory mediators [soluble glycoprotein 130 (sgp) 130, heme oxidase-1 (HO-1) and IL-10] and biomarkers for neurodevelopment [brain-derived neurotrophic factor (BDNF)], and oxidative stress [8-isoprostane (8-IsoP)] by the placenta. Methods Placental explant cultures were treated with BPA (0–10,000 nM) in the presence or absence of 107 colony-forming unit (CFU)/mL heat-killed Escherichia coli for 24 h. Biomarker concentrations in conditioned medium were quantified by the enzyme-linked immunosorbent assay (ELISA). Results Under basal conditions, IL-1β and IL-6 production was enhanced by BPA in a dose-dependent manner. Sgp130, a soluble receptor that reduces IL-6 bioactivity, was suppressed by BPA at 1000–10,000 nM. BPA also enhanced BDNF production at 1000 and 10,000 nM, and 8-IsoP expression at 10 and 100 nM. For bacteria-treated cultures, BPA increased IL-6 production at 100 nM and reduced sgp130 at 1000 nM but had no effect on IL-1β, TNF-α, BDNF, HO-1, 8-IsoP or IL-10 production. Conclusion BPA may increase placental inflammation by promoting IL-1β and IL-6 but inhibiting sgp130. It may also disrupt oxidative balance and neurodevelopment by increasing 8-IsoP and BDNF production.

scholarly journals Local interaction of prostaglandin F2α with endothelin-1 and tumor necrosis factor-α on the release of progesterone and oxytocin in ovine corpora lutea in vivo: a possible implication for a luteolytic cascade

Reproduction ◽  
2004 ◽  
Vol 127 (1) ◽  
pp. 117-124 ◽  
Author(s):  
M Ohtani ◽  
S Takase ◽  
M P B Wijayagunawardane ◽  
M Tetsuka ◽  
A Miyamoto
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Prostaglandin F2α ◽  
Corpora Lutea ◽  
Dependent Manner ◽  
Endothelin 1 ◽  
Factor Α ◽  
Necrosis Factor

Endothelin-1 (ET-1) and tumor necrosis factor-α (TNFα) participate in the cascade of luteolysis. Thus, in the present study the interactions of ET-1 and TNFα with prostaglandin F2α (PGF2α) on the release of progesterone and oxytocin (OT) within the corpus luteum (CL) were investigated. A microdialysis system (MDS) was surgically implanted in ovine CL (one MDS line/CL; 5–10 lines/ewe) formed after super-ovulation. A 4-h perfusion with PGF2α (0.01–1 μmol l −1) induced no clear effect on progesterone release, but acutely stimulated OT release in a dose-dependent manner. A perfusion of PGF2α (1 μmol l −1) increased ET-1 release over a period of 12 h. Two perfusions of ET-1 (0.1 μmol l−1) or a perfusion of ET-1 followed by TNFα (200 ng ml−1) decreased progesterone release (56–64% at 36–48 h). When the CL were pre-perfused with PGF2α (1 μmol l−1), two consecutive perfusions of ET-1 decreased progesterone release more rapidly. Similarly, a pre-perfusion with PGF2α followed by consecutive perfusions of ET-1 and then TNFα rapidly decreased progesterone release, with the inhibition most pronounced (35%) at 36–48 h. The simultaneous infusion of ET-1 with PGF2α induced a rapid decrease in progesterone release (36% at 36–48 h). In a further study, the possible second messenger systems involved in PGF2α action on the release of progesterone, OT and ET-1 were investigated. A perfusion with 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 10 μmol l−1), A23187 (10 μmol l−1), or PGF2α + A23187 increased progesterone release during infusion, but decreased it after perfusion. All treatments induced a massive release of OT during infusion, and increased ET-1 release after infusion. These results show that ET-1 is capable of suppressing progesterone release in the PGF2α-primed ovine CL in vivo and thus ET-1 works as a local luteolysin together with PGF2α during the process of functional luteolysis. During structural luteolysis, TNFα may interact with PGF2α and ET-1 to cause a rapid drop in progesterone release and accelerate the process of luteolysis. This result supports the contention that ET-1 and TNFα interact with PGF2α as local luteolytic mediators in the ewe as previously suggested.

scholarly journals Turnour necrosis factor stimulates endothelin-1 gene expression in cultured bovine endothelial cells

1992 ◽  
Vol 1 (4) ◽  
pp. 263-266 ◽  
Author(s):  
Silvia Orisio ◽  
Marina Morigi ◽  
Carla Zoja ◽  
Norberto Perico ◽  
Giuseppe Remuzzi
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Hypotensive Effect ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Aortic Endothelial Cells ◽  
Endothelin 1 ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

We have studied the effect of human recombinant tumour necrosis factor-α (TNF-α) on gene expression and production of endothelin-1 in cultured bovine aortic endothelial cells. TNF-α (10 and 100 ng ml−1) increased in a time dependent manner the preproendothelin-1 mRNA levels in respect to unstimulated endothelial cells. TNF-α induced endothelin-1 gene expression was associated with a parallel increase in the release of the corresponding peptide in the culture medium. These findings suggest that the enhanced synthesis and release of endothelin-1 occurring in conditions of increased generation of TNF, may act as a modulatory factor that counteracts the hypotensive effect and the excessive platelet aggregation and adhesion induced by TNF.

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