scholarly journals Facilitation of IL-22 production from innate lymphoid cells by prostaglandin E2 prevents experimental lung neutrophilic inflammation

Thorax ◽  
2018 ◽  
Vol 73 (11) ◽  
pp. 1081-1084 ◽  
Author(s):  
Jennifer M Felton ◽  
Rodger Duffin ◽  
Calum T Robb ◽  
Siobhan Crittenden ◽  
Stephen M Anderton ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Inflammation ◽  
Innate Lymphoid Cells ◽  
Therapeutic Strategies ◽  
Lymphoid Cells ◽  
Acute Injury ◽  
Prostaglandin E ◽  
Acute Lung Inflammation ◽  
Neutrophilic Inflammation ◽  
Life Threatening

Acute lung injury is a neutrophil-dominant, life-threatening disease without effective therapies and better understanding of the pathophysiological mechanisms involved is an urgent need. Here we show that interleukin (IL)-22 is produced from innate lymphoid cells (ILC) and is responsible for suppression of experimental lung neutrophilic inflammation. Blocking prostaglandin E2 (PGE2) synthesis reduces lung ILCs and IL-22 production, resulting in exacerbation of lung neutrophilic inflammation. In contrast, activation of the PGE2 receptor EP4 prevents acute lung inflammation. We thus demonstrate a mechanism for production of innate IL-22 in the lung during acute injury, highlighting potential therapeutic strategies for control of lung neutrophilic inflammation by targeting the PGE2/ILC/IL-22 axis.

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 Pretreatment with atorvastatin ameliorates cobra venom factor-induced acute lung inflammation in mice

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jing Guo ◽  
Min Li ◽  
Yi Yang ◽  
Lin Zhang ◽  
Li-wei Zhang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Protein Content ◽  
Complement System ◽  
Complement Activation ◽  
Lung Inflammation ◽  
Acute Lung Inflammation ◽  
Tnf Α ◽  
The Complement System

Abstract Background The complement system plays a critical role as the pathogenic factor in the models of acute lung injury due to various causes. Cobra venom factor (CVF) is a commonly used complement research tool. The CVF can cause acute inflammation in the lung by producing complement activation components. Atorvastatin (ATR) is a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor approved for control of plasma cholesterol levels. This inhibitor can reduce the acute pulmonary inflammatory response. However, the ability of ATR in treating acute lung inflammation caused by complement activation is still unknown. Therefore, we investigated the effect of ATR on lung inflammation in mice induced by activation of the complement alternative pathway in this study. Methods ATR (10 mg/kg/day via oral gavage) was administered for 7 days before tail vein injection of CVF (25 μg/kg). On the seventh day, all mice were sacrificed 1 h after injection. The lung lobe, bronchoalveolar lavage fluid (BALF), and blood samples were collected. The myeloperoxidase (MPO) activity of the lung homogenate, the leukocyte cell count, and the protein content of BALF were measured. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), P-selectin, and Intercellular cell adhesion molecule-1 (ICAM-1) in BALF and serum were determined by enzyme-linked immunosorbent assay. The pathological change of the lung tissue was observed by hematoxylin and eosin staining. The deposition of C5b-9 in the lung tissue was detected by immunohistochemistry. The phosphorylation of NF-κB p65 in the lung tissues was examined by immunohistochemistry and western blotting. Results The lung inflammation levels were determined by measuring the leukocyte cell numbers and protein content of BALF, the lung MPO activity, and expression and staining of the inflammatory mediators (IL-6 and TNF-α), and adhesion molecules (P-selectin and ICAM-1) for lung lesion. A significant reduction in the lung inflammation levels was observed after 7 days in ATR pre-treated mice with a CVF-induced lung disease. Deposition of C5b-9 was significantly alleviated by ATR pretreatment. Early intervention with ATR significantly reduced the development of acute lung inflammation on the basis of phosphorylation of NF-κB p65 in the lung. Conclusion These findings suggest the identification of ATR treatment for the lung inflammation induced by activating the complement system on the basis of its anti-inflammatory response. Together with the model replicating the complement activating characteristics of acute lung injury, the results may be translatable to the overactivated complement relevant diseases.

scholarly journals NK Cells Alleviate Lung Inflammation by Negatively Regulating Group 2 Innate Lymphoid Cells

2017 ◽  
Vol 198 (8) ◽  
pp. 3336-3344 ◽  
Author(s):  
Jiacheng Bi ◽  
Lulu Cui ◽  
Guang Yu ◽  
Xiaolu Yang ◽  
Youhai Chen ◽  
...  
Keyword(s):  
Nk Cells ◽  
Lung Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Group 2

scholarly journals Activation of NF-κB signaling in rare earth neodymium oxide particle-induced acute lung injury

2015 ◽  
Vol 4 (6) ◽  
pp. 1587-1596 ◽  
Author(s):  
Suhua Wang ◽  
Yanrong Gao ◽  
Lihua Huang ◽  
Shanshan Zheng ◽  
Chunxia Wang ◽  
...  
Keyword(s):  
Rare Earth ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Lung Inflammation ◽  
Oxide Particle ◽  
Neodymium Oxide ◽  
Activation Mechanism ◽  
Acute Lung Inflammation

The activation mechanism of the NF-κB signaling pathway in Nd2O3exposure-induced acute lung inflammation and pneumoconiosis.

scholarly journals Androgen signaling negatively controls group 2 innate lymphoid cells

2017 ◽  
Vol 214 (6) ◽  
pp. 1581-1592 ◽  
Author(s):  
Sophie Laffont ◽  
Eve Blanquart ◽  
Magali Savignac ◽  
Claire Cénac ◽  
Gilles Laverny ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Lung Inflammation ◽  
Inflammatory Responses ◽  
Allergic Airway Inflammation ◽  
Innate Lymphoid Cells ◽  
Protective Role ◽  
Lymphoid Cells ◽  
Peripheral Tissues ◽  
Group 2

Prevalence of asthma is higher in women than in men, but the mechanisms underlying this sex bias are unknown. Group 2 innate lymphoid cells (ILC2s) are key regulators of type 2 inflammatory responses. Here, we show that ILC2 development is greatly influenced by male sex hormones. Male mice have reduced numbers of ILC2 progenitors (ILC2Ps) and mature ILC2s in peripheral tissues compared with females. In consequence, males exhibit reduced susceptibility to allergic airway inflammation in response to environmental allergens and less severe IL-33–driven lung inflammation, correlating with an impaired expansion of lung ILC2s. Importantly, orchiectomy, but not ovariectomy, abolishes the sex differences in ILC2 development and restores IL-33–mediated lung inflammation. ILC2Ps express the androgen receptor (AR), and AR signaling inhibits their differentiation into mature ILC2s. Finally, we show that hematopoietic AR expression limits IL-33–driven lung inflammation through a cell-intrinsic inhibition of ILC2 expansion. Thus, androgens play a crucial protective role in type 2 airway inflammation by negatively regulating ILC2 homeostasis, thereby limiting their capacity to expand locally in response to IL-33.

scholarly journals Group 2 Innate Lymphoid Cells Are Critical for the Initiation of Adaptive T Helper 2 Cell-Mediated Allergic Lung Inflammation

Immunity ◽  
2014 ◽  
Vol 40 (3) ◽  
pp. 425-435 ◽  
Author(s):  
Timotheus Y.F. Halim ◽  
Catherine A. Steer ◽  
Laura Mathä ◽  
Matthew J. Gold ◽  
Itziar Martinez-Gonzalez ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
T Helper ◽  
T Helper 2 ◽  
Allergic Lung Inflammation ◽  
Group 2

scholarly journals IL-17–producing ST2+ group 2 innate lymphoid cells play a pathogenic role in lung inflammation

2019 ◽  
Vol 143 (1) ◽  
pp. 229-244.e9 ◽  
Author(s):  
Ting Cai ◽  
Jinxin Qiu ◽  
Yan Ji ◽  
Wenjing Li ◽  
Zhaoyun Ding ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Pathogenic Role ◽  
Group 2

scholarly journals The Role of Innate Lymphoid Cells in the Regulation of Immune Homeostasis in Sepsis-Mediated Lung Inflammation

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 808
Author(s):  
Yuichi Akama ◽  
Naoko Satoh-Takayama ◽  
Eiji Kawamoto ◽  
Atsushi Ito ◽  
Arong Gaowa ◽  
...  
Keyword(s):  
Septic Shock ◽  
Lung Injury ◽  
Immune Cells ◽  
Lung Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
System Response ◽  
Immune Homeostasis ◽  
Type 2 Cytokines

Septic shock/severe sepsis is a deregulated host immune system response to infection that leads to life-threatening organ dysfunction. Lung inflammation as a form of acute lung injury (ALI) is often induced in septic shock. Whereas macrophages and neutrophils have been implicated as the principal immune cells regulating lung inflammation, group two innate lymphoid cells (ILC2s) have recently been identified as a new player regulating immune homeostasis. ILC2 is one of the three major ILC subsets (ILC1s, ILC2s, and ILC3s) comprised of newly identified innate immune cells. These cells are characterized by their ability to rapidly produce type 2 cytokines. ILC2s are predominant resident ILCs and, thereby, have the ability to respond to signals from damaged tissues. ILC2s regulate the immune response, and ILC2-derived type 2 cytokines may exert protective roles against sepsis-induced lung injury. This focused review not only provides readers with new insights into the signaling mechanisms by which ILC2s modulate sepsis-induced lung inflammation, but also proposes ILC2 as a novel therapeutic target for sepsis-induced ALI.

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