scholarly journals Apoptosis signal-regulating kinase-1 promotes inflammasome priming in macrophages

2019 ◽  
Vol 316 (3) ◽  
pp. L418-L427 ◽  
Author(s):  
Camille N. Immanuel ◽  
Bin Teng ◽  
Brittany Dong ◽  
Elizabeth M. Gordon ◽  
Joseph A. Kennedy ◽  
...  
Keyword(s):  
Lung Injury ◽  
Neutrophil Infiltration ◽  
Response To Treatment ◽  
Wild Type ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Proinflammatory Response ◽  
Caspase 1 ◽  
Ventilator Induced Lung Injury ◽  
First Time

We previously showed that mice deficient in apoptosis signal-regulating kinase-1 (ASK1) were partially protected against ventilator-induced lung injury. Because ASK1 can promote both cell death and inflammation, we hypothesized that ASK1 activation regulates inflammasome-mediated inflammation. Mice deficient in ASK1 expression (ASK1−/−) exhibited significantly less inflammation and lung injury (as measured by neutrophil infiltration, IL-6, and IL-1β) in response to treatment with inhaled lipopolysaccharide (LPS) compared with wild-type (WT) mice. To determine whether this proinflammatory response was mediated by ASK1, we investigated inflammasome-mediated responses to LPS in primary macrophages and bone marrow-derived macrophages (BMDMs) from WT and ASK1−/− mice, as well as the mouse alveolar macrophage cell line MH-S. Cells were treated with LPS alone for priming or LPS followed by ATP for activation. When macrophages were stimulated with LPS followed by ATP to activate the inflammasome, we found a significant increase in secreted IL-1β from WT cells compared with ASK1-deficient cells. LPS priming stimulated an increase in NOD-like receptor 3 (NLRP3) and pro-IL-1β in WT BMDMs, but expression of NLRP3 was significantly decreased in ASK1−/− BMDMs. Subsequent ATP treatment stimulated an increase in cleaved caspase-1 and IL-1β in WT BMDMs compared with ASK1−/− BMDMs. Similarly, treatment of MH-S cells with LPS + ATP caused an increase in both cleaved caspase-1 and IL-1β that was diminished by the ASK-1 inhibitor NQDI1. These results demonstrate, for the first time, that ASK1 promotes inflammasome priming.

Class B Scavenger Receptors BI and BII Protect Against LPS-induced Acute Lung Injury in Mice by Mediating LPS Clearance

2021 ◽  
Author(s):  
Irina N. Baranova ◽  
Alexander V. Bocharov ◽  
Tatyana G. Vishnyakova ◽  
Zhigang Chen ◽  
Anna A. Birukova ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Transgenic Mice ◽  
Neutrophil Infiltration ◽  
Lavage Fluid ◽  
Protective Role ◽  
Lung Damage ◽  
Wild Type ◽  
Class B ◽  
Anti Inflammatory

Recent studies suggest an anti-inflammatory protective role for class B scavenger receptor BI (SR-BI) in endotoxin-induced inflammation and sepsis. Other data, including ours, provide evidence for an alternative role of SR-BI, facilitating bacterial and endotoxin uptake, and contributing to inflammation and bacterial infection. Enhanced endotoxin susceptibility of SR-BI deficient mice due to their anti-inflammatory glucocorticoid deficiency complicates understanding SR-BI’s role in endotoxemia/sepsis, calling for use of alternative models. In this study, using hSR-BI and hSR-BII transgenic mice, we found that SR-BI and to a lesser extent its splicing variant SR-BII, protects against LPS-induced lung damage. At 20 hours after intratracheal LPS instillation the extent of pulmonary inflammation and vascular leakage was significantly lower in hSR-BI and hSR-BII transgenic mice compared to wild type mice. Higher bronchoalveolar lavage fluid (BALF) inflammatory cell count and protein content as well as lung tissue neutrophil infiltration found in wild type mice was associated with markedly (2-3 times) increased pro-inflammatory cytokine production as compared to transgenic mice following LPS administration. Markedly lower endotoxin levels detected in BALF of transgenic vs. wild type mice along with the significantly increased BODIPY-LPS uptake observed in lungs of hSR-BI and hSR-BII mice 20 hours after the IT LPS injection suggest that hSR-BI and hSR-BII-mediated enhanced LPS clearance in the airways could represent the mechanism of their protective role against LPS-induced acute lung injury.

Inhibition of matrix metalloproteinase-9 prevents neutrophilic inflammation in ventilator-induced lung injury

2006 ◽  
Vol 291 (4) ◽  
pp. L580-L587 ◽  
Author(s):  
Je Hyeong Kim ◽  
Min Hyun Suk ◽  
Dae Wui Yoon ◽  
Seung Heon Lee ◽  
Gyu Young Hur ◽  
...  
Keyword(s):  
Lung Injury ◽  
Matrix Metalloproteinase ◽  
Tidal Volume ◽  
Weight Ratio ◽  
Dry Weight ◽  
Neutrophil Infiltration ◽  
Neutrophilic Inflammation ◽  
Ventilator Induced Lung Injury ◽  
Metalloproteinase 9 ◽  
Expression And Activity

Neutrophils are considered to play a central role in ventilator-induced lung injury (VILI). However, the pulmonary consequences of neutrophil accumulation have not been fully elucidated. Matrix metalloproteinase-9 (MMP-9) had been postulated to participate in neutrophil transmigration. The purpose of this study was to investigate the role of MMP-9 in the neutrophilic inflammation of VILI. Male Sprague-Dawley rats were divided into three groups: 1) low tidal volume (LVT), 7 ml/kg of tidal volume (VT); 2) high tidal volume (HVT), 30 ml/kg of VT; and 3) HVT with MMP inhibitor (HVT+MMPI). As a MMPI, CMT-3 was administered daily from 3 days before mechanical ventilation. Degree of VILI was assessed by wet-to-dry weight ratio and acute lung injury (ALI) scores. Neutrophilic inflammation was determined from the neutrophil count in the lung tissue and myeloperoxidase (MPO) activity in the bronchoalveolar lavage fluid (BALF). MMP-9 expression and activity were examined by immunohistochemical staining and gelatinase zymography, respectively. The wet-to-dry weight ratio, ALI score, neutrophil infiltration, and MPO activity were increased significantly in the HVT group. However, in the HVT+MMPI group, pretreatment with MMPI decreased significantly the degree of VILI, as well as neutrophil infiltration and MPO activity. These changes correlated significantly with MMP-9 immunoreactivity and MMP-9 activity. Most outcomes were significantly worse in the HVT+MMPI group compared with the LVT group. In conclusion, VILI mediated by neutrophilic inflammation is closely related to MMP-9 expression and activity. The inhibition of MMP-9 protects against the development of VILI through the downregulation of neutrophil-mediated inflammation.

Ventilator-Induced Lung Injury Is Associated with Neutrophil Infiltration, Macrophage Activation, and TGF-β1 mRNA Upregulation in Rat Lungs

2001 ◽  
Vol 92 (2) ◽  
pp. 428-436 ◽  
Author(s):  
Hideaki Imanaka ◽  
Motomu Shimaoka ◽  
Nariaki Matsuura ◽  
Masaji Nishimura ◽  
Noriyuki Ohta ◽  
...  
Keyword(s):  
Lung Injury ◽  
Macrophage Activation ◽  
Neutrophil Infiltration ◽  
Ventilator Induced Lung Injury ◽  
Rat Lungs ◽  
Tgf Β1

Low-level iron-dependent mutants ofListeria monocytogenesand their virulence in macrophages

2003 ◽  
Vol 49 (2) ◽  
pp. 78-84 ◽  
Author(s):  
Philippe Andre ◽  
Stéphanie Oberle ◽  
Véronique Specklin ◽  
Yves Lombard ◽  
Dominique Jean-Marie Vidon
Keyword(s):  
Listeria Monocytogenes ◽  
Cell Line ◽  
Parental Strain ◽  
Wild Strain ◽  
Wild Type ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Macrophage Cells ◽  
J774 Macrophage ◽  
Iron Requirement

Listeria monocytogenes is an opportunistic intracellular pathogen capable of growth within phagocytic cells that requires iron for growth and virulence expression. In the presence of an appropriate concentration of tropolone, an iron-chelating agent, growth of L. monocytogenes is completely inhibited. However, this inhibition can be relieved by addition of dopamine, norepinephrine, or ferric citrate. By selection on streptonigrin medium supplemented with tropolone and norepinephrine, we have obtained two spontaneous mutants, Lm-8 and Lm-15, with the same iron dependence but lower iron dependence than the wild-type Lm-B38. The association between iron requirement and virulence of the two mutants and the wild type was studied in the J774 macrophage cell line. One hour after phagocytosis by the J774 macrophage cell line, the two mutants and the parental strain displayed no difference in the number of phagocytosed bacteria. Twenty-four hours after phagocytosis, the number of bacteria within the surviving macrophages was identical for the wild strain and the two clones. However, only 40% of macrophage cells infected with Lm-8 and 90% of those infected with Lm-15 were alive after 24 h in comparison with macrophage cells infected with the parental strain Lm-B38. These data demonstrate that there is no direct correlation between iron requirement and virulence of L. monocytogenes in the J774 macrophage cell line.Key words: Listeria monocytogenes, iron, virulence, macrophages.

scholarly journals Correction: Nicotinamide Exacerbates Hypoxemia in Ventilator-Induced Lung Injury Independent of Neutrophil Infiltration

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0128735 ◽  
Author(s):  
Heather D. Jones ◽  
Jeena Yoo ◽  
Timothy R. Crother ◽  
Pierre Kyme ◽  
Anat Ben-Shlomo ◽  
...  
Keyword(s):  
Lung Injury ◽  
Neutrophil Infiltration ◽  
Ventilator Induced Lung Injury

scholarly journals Interaction of Bartonella henselae with the Murine Macrophage Cell Line J774: Infection and Proinflammatory Response

2001 ◽  
Vol 69 (10) ◽  
pp. 5974-5980 ◽  
Author(s):  
Tiziana Musso ◽  
Raffaele Badolato ◽  
Daniela Ravarino ◽  
Sarah Stornello ◽  
Patrizia Panzanelli ◽  
...  
Keyword(s):  
Cell Line ◽  
Bartonella Henselae ◽  
Competitive Inhibitor ◽  
No Production ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Proinflammatory Response ◽  
Necrosis Factor Alpha ◽  
Ifn Γ ◽  
Limiting Condition

ABSTRACT Bartonella henselae is the causative agent of cat scratch disease (CSD), a self-limiting condition characterized by a subacute regional lymphadenopathy that may develop into disseminated bartonellosis in immunocompromised subjects. Mice experimentally infected with B. henselaedisplay typical liver and spleen granulomas rich in T cells and macrophages. So far there are no data on the interaction between bartonellae and macrophages. In order to clarify this topic, we investigated the interaction of B. henselae with J774, a mouse macrophage cell line. Analysis of bacterial uptake by functional assays and transmission electron microscopy indicates that bartonellae can enter and survive inside J774. Entry occurred within 30 min postinfection and reached a plateau at 160 min. Infection of J774 was followed by a dose-dependent release of the proinflammatory cytokines tumor necrosis factor alpha, interleukin 1β (IL-1β), and IL-6. Bartonellae persisted intracellularly without loss of viability for at least 8 h, and their number slightly decreased 24 h postinfection. Gamma interferon (IFN-γ) treatment of J774 significantly decreased the number of recoverable bacteria at 8 and 24 h. This enhancement of macrophage bactericidal activity was associated with nitric oxide (NO) release and was prevented by the addition of the competitive inhibitor of NO synthesis NG -monomethyll-arginine. These findings suggest that IFN-γ-mediated activation of macrophages may be important for the clearing ofB. henselae infection and that anti-B. henselae microbicidal activity of IFN-γ-activated macrophages is mediated to a large extent by NO production.

scholarly journals Novel Arsenic Nanoparticles Are More Effective and Less Toxic than As (III) to Inhibit Extracellular and Intracellular Proliferation ofLeishmania donovani

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Sudipta Chakraborty ◽  
Kaushik Bhar ◽  
Sandip Saha ◽  
Rajarshi Chakrabarti ◽  
Anjali Pal ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Protozoan Parasite ◽  
Antileishmanial Activity ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Vector Borne ◽  
First Time ◽  
Intracellular Proliferation ◽  
Mouse Macrophage Cell Line

Visceral leishmaniasis, a vector-borne tropical disease that is threatening about 350 million people worldwide, is caused by the protozoan parasiteLeishmania donovani. Metalloids like arsenic and antimony have been used to treat diseases like leishmaniasis caused by the kinetoplastid parasites. Arsenic (III) at a relatively higher concentration (30 μg/mL) has been shown to have antileishmanial activity, but this concentration is reported to be toxic in several experimental mammalian systems. Nanosized metal (0) particles have been shown to be more effective than their higher oxidation state forms. There is no information so far regarding arsenic nanoparticles (As-NPs) as an antileishmanial agent. We have tested the antileishmanial properties of the As-NPs, developed for the first time in our laboratory. As-NPs inhibited thein vitrogrowth, oxygen consumption, infectivity, and intramacrophage proliferation ofL. donovaniparasites at a concentration which is about several fold lower than that of As (III). Moreover, this antileishmanial activity has comparatively less cytotoxic effect on the mouse macrophage cell line. It is evident from our findings that As-NPs have more potential than As (III) to be used as an antileishmanial agent.

Clara cell secretory protein and phospholipase A2 activity modulate acute ventilator-induced lung injury in mice

2005 ◽  
Vol 98 (4) ◽  
pp. 1264-1271 ◽  
Author(s):  
Sawako Yoshikawa ◽  
Takashige Miyahara ◽  
Susan D. Reynolds ◽  
Barry R. Stripp ◽  
Mircea Anghelescu ◽  
...  
Keyword(s):  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Dry Weight ◽  
High Volume ◽  
Secretory Protein ◽  
Clara Cell ◽  
Wild Type ◽  
Clara Cell Secretory Protein ◽  
Ventilator Induced Lung Injury ◽  
Volume Ventilation

Lung vascular permeability is acutely increased by high-pressure and high-volume ventilation. To determine the roles of mechanically activated cytosolic PLA2 (cPLA2) and Clara cell secretory protein (CCSP), a modulator of cPLA2 activity, we compared lung injury with and without a PLA2 inhibitor in wild-type mice and CCSP-null mice (CCSP−/−) ventilated with high and low peak inflation pressures (PIP) for 2- or 4-h periods. After ventilation with high PIP, we observed significant increases in the bronchoalveolar lavage albumin concentrations, lung wet-to-dry weight ratios, and lung myeloperoxidase in both genotypes compared with unventilated controls and low-PIP ventilated mice. All injury variables except myeloperoxidase were significantly greater in the CCSP−/− mice relative to wild-type mice. Inhibition of cPLA2 in wild-type and CCSP−/− mice ventilated at high PIP for 4 h significantly reduced bronchoalveolar lavage albumin and total protein and lung wet-to-dry weight ratios compared with vehicle-treated mice of the same genotype. Membrane phospho-cPLA2 and cPLA2 activities were significantly elevated in lung homogenates of high-PIP ventilated mice of both genotypes but were significantly higher in the CCSP−/− mice relative to the wild-type mice. Inhibition of cPLA2 significantly attenuated both the phospho-cPLA2 increase and increased cPLA2 activity due to high-PIP ventilation. We propose that mechanical activation of the cPLA2 pathway contributes to acute high PIP-induced lung injury and that CCSP may reduce this injury through inhibition of the cPLA2 pathway and reduction of proinflammatory products produced by this pathway.

scholarly journals Respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness

2015 ◽  
Vol 309 (3) ◽  
pp. L205-L210 ◽  
Author(s):  
Weifeng Song ◽  
Zhihong Yu ◽  
Stephen F. Doran ◽  
Namasivayam Ambalavanan ◽  
Chad Steele ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Lung Injury ◽  
Airway Hyperresponsiveness ◽  
Neutrophil Infiltration ◽  
Lavage Fluid ◽  
Infection Model ◽  
Type 2 Cytokines ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
First Time

Exposure to chlorine (Cl2) damages airway and alveolar epithelia resulting in acute lung injury and reactive airway hyperresponsiveness (AHR) to methacholine. However, little is known about the effect of preexisting respiratory disease on Cl2-induced lung injury. By using a murine respiratory syncytial virus (RSV) infection model, we found that preexisting RSV infection increases Cl2 (187 ppm for 30 min)-induced lung inflammation and airway AHR at 24 h after exposure (5 days after infection). RSV infection and Cl2 exposure synergistically induced oxygen desaturation and neutrophil infiltration and increased MCP-1, MIP-1β, IL-10, IFN-γ, and RANTES concentrations in the bronchoalveolar lavage fluid (BALF). In contrast, levels of type 2 cytokines (i.e., IL-4, IL-5, IL-9, and IL-13) were not significantly affected by either RSV infection or Cl2 exposure. Cl2 exposure, but not RSV infection, induced AHR to methacholine challenge as measured by flexiVent. Moreover, preexisting RSV infection amplified BALF levels of hyaluronan (HA) and AHR. The Cl2-induced AHR was mitigated by treatment with inter-α-trypsin inhibitor antibody, which inhibits HA signaling, suggesting a mechanism of HA-mediated AHR from exacerbated oxidative injury. Our results show for the first time that preexisting RSV infection predisposes the lung to Cl2-induced injury. These data emphasize the necessity for further research on the effects of Cl2 in vulnerable populations and the development of appropriate treatments.

scholarly journals Plasminogen Activator Inhibitor-Type I Gene Deficient Mice Show Reduced Influx of Neutrophils in Ventilator-Induced Lung Injury

2011 ◽  
Vol 2011 ◽  
pp. 1-11
Author(s):  
Esther K. Wolthuis ◽  
Alexander P. J. Vlaar ◽  
Jorrit-Jan H. Hofstra ◽  
Joris J. T. H. Roelofs ◽  
Vivian de Waard ◽  
...  
Keyword(s):  
Lung Injury ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Lavage Fluid ◽  
Type I ◽  
Wild Type ◽  
Ventilator Induced Lung Injury ◽  
Deficient Mice ◽  
Activator Inhibitor ◽  
Pai 1

Ventilator-induced lung injury (VILI) is associated with inhibition of the fibrinolytic system secondary to increased production of plasminogen activator inhibitor- (PAI-)1. To determine the role of PAI-1 on pulmonary coagulopathy and inflammation during mechanical ventilation, PAI-1 gene-deficient mice and their wild-type littermates were anesthetized (control), or anesthetized, tracheotomized and subsequently ventilated for 5 hours with either low tidal volumes () or high tidal volumes (). VILI was assessed by pulmonary coagulopathy, lung wet-to-dry ratios, total protein level in bronchoalveolar lavage fluid, neutrophil influx, histopathology, and pulmonary and plasma cytokine levels. Ventilation resulted in pulmonary coagulopathy and inflammation, with more injury following ventilation with as compared to . In PAI-1 gene-deficient mice, the influx of neutrophils in the pulmonary compartment was attenuated, while increased levels of pulmonary cytokines were found. Other endpoints of VILI were not different between PAI-1 gene-deficient and wild-type mice. These data indicate that a defect fibrinolytic response attenuates recruitment of neutrophils in VILI.

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