scholarly journals Siglec-E is a negative regulator of acute pulmonary neutrophil inflammation and suppresses CD11b β2-integrin–dependent signaling

Blood ◽  
2013 ◽  
Vol 121 (11) ◽  
pp. 2084-2094 ◽  
Author(s):  
Sarah J. McMillan ◽  
Ritu S. Sharma ◽  
Emma J. McKenzie ◽  
Hannah E. Richards ◽  
Jiquan Zhang ◽  
...  
Keyword(s):  
Lung Disease ◽  
Lung Inflammation ◽  
Potential Role ◽  
Neutrophil Recruitment ◽  
Negative Regulator ◽  
Acute Lung Inflammation ◽  
Inflammatory Lung Disease ◽  
Β2 Integrin ◽  
Key Points

Key Points First report describing in vivo function of siglec-E as a negative regulator of neutrophil recruitment in acute lung inflammation. Implications for the human functional ortholog, siglec-9, and its potential role in regulating inflammatory lung disease.

scholarly journals Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots

Nanomaterials ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 180
Author(s):  
Maud Weiss ◽  
Jiahui Fan ◽  
Mickaël Claudel ◽  
Luc Lebeau ◽  
Françoise Pons ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Lung Inflammation ◽  
Adverse Outcome ◽  
Cellular Responses ◽  
Target Cells ◽  
Inflammasome Activation ◽  
Adverse Outcome Pathway ◽  
Acute Lung Inflammation

With the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of NP toxicity, and hence hopefully predict the health risks associated with NP exposure. Herein, we propose a putative AOP for the lung toxicity of NPs using emerging nanomaterials called carbon dots (CDs), and in vivo and in vitro experimental approaches. We first investigated the effect of a single administration of CDs on mouse airways. We showed that CDs induce an acute lung inflammation and identified airway macrophages as target cells of CDs. Then, we studied the cellular responses induced by CDs in an in vitro model of macrophages. We observed that CDs are internalized by these cells (molecular initial event) and induce a series of key events, including loss of lysosomal integrity and mitochondrial disruption (organelle responses), as well as oxidative stress, inflammasome activation, inflammatory cytokine upregulation and macrophage death (cellular responses). All these effects triggering lung inflammation as tissular response may lead to acute lung injury.

scholarly journals The Crucial Role of PPARγ-Egr-1-Pro-Inflammatory Mediators Axis in IgG Immune Complex-Induced Acute Lung Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunguang Yan ◽  
Jing Chen ◽  
Yue Ding ◽  
Zetian Zhou ◽  
Bingyu Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Immune Complex ◽  
Inflammatory Mediators ◽  
Lung Inflammation ◽  
Acute Lung Inflammation ◽  
Pparγ Agonist

BackgroundThe ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR) γ plays crucial roles in diverse biological processes including cellular metabolism, differentiation, development, and immune response. However, during IgG immune complex (IgG-IC)-induced acute lung inflammation, its expression and function in the pulmonary tissue remains unknown.ObjectivesThe study is designed to determine the effect of PPARγ on IgG-IC-triggered acute lung inflammation, and the underlying mechanisms, which might provide theoretical basis for therapy of acute lung inflammation.SettingDepartment of Pathogenic Biology and Immunology, Medical School of Southeast UniversitySubjectsMice with down-regulated/up-regulated PPARγ activity or down-regulation of Early growth response protein 1 (Egr-1) expression, and the corresponding controls.InterventionsAcute lung inflammation is induced in the mice by airway deposition of IgG-IC. Activation of PPARγ is achieved by using its agonist Rosiglitazone or adenoviral vectors that could mediate overexpression of PPARγ. PPARγ activity is suppressed by application of its antagonist GW9662 or shRNA. Egr-1 expression is down-regulated by using the gene specific shRNA.Measures and Main ResultsWe find that during IgG-IC-induced acute lung inflammation, PPARγ expression at both RNA and protein levels is repressed, which is consistent with the results obtained from macrophages treated with IgG-IC. Furthermore, both in vivo and in vitro data show that PPARγ activation reduces IgG-IC-mediated pro-inflammatory mediators’ production, thereby alleviating lung injury. In terms of mechanism, we observe that the generation of Egr-1 elicited by IgG-IC is inhibited by PPARγ. As an important transcription factor, Egr-1 transcription is substantially increased by IgG-IC in both in vivo and in vitro studies, leading to augmented protein expression, thus amplifying IgG-IC-triggered expressions of inflammatory factors via association with their promoters.ConclusionDuring IgG-IC-stimulated acute lung inflammation, PPARγ activation can relieve the inflammatory response by suppressing the expression of its downstream target Egr-1 that directly binds to the promoter regions of several inflammation-associated genes. Therefore, regulation of PPARγ-Egr-1-pro-inflammatory mediators axis by PPARγ agonist Rosiglitazone may represent a novel strategy for blockade of acute lung injury.

scholarly journals Toll-Interacting Protein, Tollip, Inhibits IL-13-Mediated Pulmonary Eosinophilic Inflammation in Mice

2018 ◽  
Vol 10 (2) ◽  
pp. 106-118 ◽  
Author(s):  
Yoko Ito ◽  
Niccolette Schaefer ◽  
Amelia Sanchez ◽  
David Francisco ◽  
Rafeul Alam ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Negative Regulator ◽  
Airflow Limitation ◽  
Eosinophilic Inflammation ◽  
Interacting Protein ◽  
Proinflammatory Responses ◽  
Cytokine Milieu ◽  
Underlying Mechanisms

Toll-interacting protein (Tollip) is a key negative regulator of innate immunity by preventing excessive proinflammatory responses. Tollip genetic variation has been associated with airflow limitation in asthma subjects and Tollip expression. Whether Tollip regulates lung inflammation in a type 2 cytokine milieu (e.g., IL-13) is unclear. Our goal was to determine the in vivo role of Tollip in IL-13-mediated lung eosinophilic inflammation and the underlying mechanisms. Tollip-knockout (KO) and wild-type (WT) mice were inoculated intranasally with recombinant mouse IL-13 protein to examine lung inflammation. To determine how Tollip regulates inflammation, alveolar macrophages and bone marrow-derived macrophages from Tollip KO and WT mice were cultured with or without IL-13 and/or IL-33. IL-13-treated Tollip KO mice significantly increased lung eosinophilic inflammation and eotaxin-2 (CCL24) levels compared with the WT mice. IL-13- treated Tollip KO (vs. WT) macrophages, in the absence and particularly in the presence of IL-33, increased expression of the IL-33 receptor ST2L and CCL24, which was in part dependent on enhanced activation of interleukin (IL)-1 receptor-associated kinase 1 (IRAK1) and signal transducer and activator of transcription 6 (STAT6). Our results suggest that Tollip downregulates IL-13-mediated pulmonary eosinophilia in part through inhibiting the activity of the ST2L/IL-33/IRAK1 axis and STAT6.

Role of surface complexed iron in oxidant generation and lung inflammation induced by silicates

1992 ◽  
Vol 263 (5) ◽  
pp. L511-L518 ◽  
Author(s):  
A. J. Ghio ◽  
T. P. Kennedy ◽  
A. R. Whorton ◽  
A. L. Crumbliss ◽  
G. E. Hatch ◽  
...  
Keyword(s):  
Respiratory Burst ◽  
Lung Inflammation ◽  
Important Determinant ◽  
Surface Complexation ◽  
Oxidative Degradation ◽  
Transition Metal Ions ◽  
Leukotriene B4 ◽  
Acute Lung Inflammation

Inhalation of silicates induces a variety of lung diseases in humans. The molecular mechanism(s) by which these dusts cause disease is not known. Because several naturally occurring mineral oxides have large amounts of transition metal ions on their surfaces, we tested the hypothesis that surface complexation of iron may be an important determinant of their ability to induce disease. Silica, crocidolite, kaolinite, and talc complexed considerable concentrations of Fe3+ onto their surfaces from both in vitro and in vivo sources. The potential biological importance of iron complexation was assessed by examining the relationship between surface [Fe3+] and the ability of silicates to mediate oxidative degradation of deoxyribose in vitro, induce a respiratory burst and elicit leukotriene B4 (LTB4) release by alveolar macrophages (AM) in vitro, and cause acute alveolitis after intratracheal insufflation. For these studies, three varieties of silicate dusts were used: iron-loaded, wetted (unmodified), and deferoxamine-treated to remove Fe3+. The ability of silicates to catalyze oxidant generation in an ascorbate/H2O2 system in vitro, to trigger respiratory burst activity and LTB4 release by AM, and to induce acute lung inflammation in the rat all increased with surface complexed Fe3+. The results of these studies suggest that surface complexation of iron may be an important determinant in the pathogenesis of disease after silicate exposure.

scholarly journals Effective lung-targeted RNAi in mice with peptide-based delivery of nucleic acid

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kaido Kurrikoff ◽  
Krista Freimann ◽  
Kadi-Liis Veiman ◽  
Elin Madli Peets ◽  
Andres Piirsoo ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Nucleic Acid ◽  
Lung Disease ◽  
Lung Tissue ◽  
Lung Inflammation ◽  
Disease Models ◽  
Nucleic Acid Delivery ◽  
Acute Lung Inflammation ◽  
Disease Symptoms ◽  
Targeted Gene Therapy

AbstractWe have previously developed efficient peptide-based nucleic acid delivery vectors PF14 and NF55, where we have shown that these vectors preferentially transfect lung tissue upon systemic administration with the nucleic acid. In the current work, we have explored the utilization and potential of these vectors for the lung-targeted gene therapy. Accordingly, we assessed the efficacy of these peptides in (i) two different lung disease models – acute lung inflammation and asthma in mice and (ii) using two different nucleic acid cargos – siRNA and pDNA encoding shRNA. Using RNAi against cytokine TNFα, we showed efficient anti-inflammatory effects in both disease models and observed decreased disease symptoms. Our results highlight the potential of our transfection vectors for lung gene therapy.

Depletion of pulmonary intravascular macrophages inhibits acute lung inflammation

2004 ◽  
Vol 286 (2) ◽  
pp. L363-L372 ◽  
Author(s):  
Baljit Singh ◽  
Jacqueline W. Pearce ◽  
Lakshman N. Gamage ◽  
Kyathanahalli Janardhan ◽  
Sarah Caldwell
Keyword(s):  
Lung Inflammation ◽  
Acute Inflammation ◽  
Inflammatory Cells ◽  
Acute Lung Inflammation ◽  
Tnf Α ◽  
Highly Sensitive ◽  
In Vitro Exposure ◽  
Pulmonary Intravascular Macrophages

Pulmonary intravascular macrophages (PIMs) are present in ruminants and horses. These species are highly sensitive to acute lung inflammation compared with non-PIM-containing species such as rats and humans. There is evidence that rats and humans may also recruit PIMs under certain conditions. We investigated precise contributions of PIMs to acute lung inflammation in a calf model. First, PIMs were recognized with a combination of in vivo phagocytic tracer Monastral blue and postembedding immunohistology with anti-CD68 monoclonal antibody. Second, gadolinium chloride depleted PIMs within 48 h of treatment ( P < 0.05). Finally, PIMs contain TNF-α, and their depletion reduces cells positive for IL-8 ( P < 0.05) and TNF-α ( P < 0.05) and histopathological signs of acute lung inflammation in calves infected with Mannheimia hemolytica. The majority of IL-8-positive inflammatory cells in lung septa of infected calves were platelets. Platelets from normal cattle contained preformed IL-8 that was released upon in vitro exposure to thrombin ( P < 0.05). These novel data show that PIMs, as the source of TNF-α, promote recruitment of inflammatory cells including IL-8-containing platelets to stimulate acute inflammation and pathology in lungs. These data may also be relevant to humans due to our ability to recruit PIMs.

scholarly journals Leukocyte-specific protein 1 regulates neutrophil recruitment in acute lung inflammation

2015 ◽  
Vol 309 (9) ◽  
pp. L995-L1008 ◽  
Author(s):  
Nguyen Phuong Khanh Le ◽  
Shankaramurthy Channabasappa ◽  
Mokarram Hossain ◽  
Lixin Liu ◽  
Baljit Singh
Keyword(s):  
Lung Inflammation ◽  
Neutrophil Migration ◽  
Specific Protein ◽  
Neutrophil Recruitment ◽  
Acute Lung Inflammation ◽  
Western Blots ◽  
Monocyte Chemoattractant Protein 1 ◽  
Murine Bone Marrow ◽  
Human Lungs ◽  
Activated Neutrophils

The mechanisms of excessive migration of activated neutrophils into inflamed lungs, credited with tissue damage, are not fully understood. We explored the hitherto unknown expression of leukocyte-specific protein 1 (LSP1) in human and mouse lungs and neutrophils and examined its role in neutrophil migration in acute lung inflammation. Autopsied septic human lungs showed increased LSP1 labeling in epithelium, endothelium, and leukocytes, including in their nuclei compared with normal lungs. We induced acute lung inflammation through intranasal administration of E. coli lipopolysaccharide (LPS) (80 μg) in LSP1-deficient ( Lsp1−/−) and wild-type (WT) 129/SvJ mice. Immunocytochemistry and Western blots showed increased expression of LSP1 and phosphorylated LSP1 in lungs of LPS-treated WT mice. Histology showed more congestion, inflammation, and Gr-1+neutrophils in lung of WT mice than Lsp1−/−mice. LPS-treated WT mice had significantly more neutrophils in bronchoalveolar lavage (BAL) and myeloperoxidase levels in lungs compared with Lsp1−/−mice. However, there were no differences in lung tissue and BAL concentrations of keratinocyte-derived chemokine, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α and -1β, vascular permeability, and phosphorylated p38 MAPK between LPS-treated WT and Lsp1−/−mice, whereas TNF-α concentration was higher in BAL fluid from LPS-treated WT. Immunoelectron microscopy showed increased LSP1 in the nuclei of LPS-treated neutrophils. We also found increased levels of phosphorylated LSP1 associated with plasma membrane, nucleus, and cytosol at various times after LPS treatment of murine bone marrow-derived neutrophils, suggesting its role in modulation of neutrophil cytoskeleton and the membrane. These data collectively show increased expression of LSP1 in inflamed mouse and human lungs and its role in neutrophil recruitment and lung inflammation.

scholarly journals Pulmonary Ureaplasma urealyticum Is Associated with the Development of Acute Lung Inflammation and Chronic Lung Disease in Preterm Infants

2004 ◽  
Vol 55 (1) ◽  
pp. 61-68 ◽  
Author(s):  
Sailesh Kotecha ◽  
Rachel Hodge ◽  
J Andrew Schaber ◽  
Robin Miralles ◽  
Michael Silverman ◽  
...  
Keyword(s):  
Lung Disease ◽  
Preterm Infants ◽  
Chronic Lung Disease ◽  
Lung Inflammation ◽  
Ureaplasma Urealyticum ◽  
Acute Lung Inflammation
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