scholarly journals Resolvins attenuate inflammation and promote resolution in cigarette smoke-exposed human macrophages

2015 ◽  
Vol 309 (8) ◽  
pp. L888-L901 ◽  
Author(s):  
Amanda Croasdell ◽  
Thomas H. Thatcher ◽  
R. Matthew Kottmann ◽  
Romain A. Colas ◽  
Jesmond Dalli ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Inflammatory Cytokines ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Lipid Mediators ◽  
Chronic Obstructive ◽  
M2 Macrophage ◽  
Macrophage Phenotype ◽  
Blood Monocytes ◽  
Human Macrophages

Inflammation is a protective response to injury, but it can become chronic, leading to tissue damage and disease. Cigarette smoke causes multiple inflammatory diseases, which account for thousands of deaths and cost billions of dollars annually. Cigarette smoke disrupts the function of immune cells, such as macrophages, by prolonging inflammatory signaling, promoting oxidative stress, and impairing phagocytosis, contributing to increased incidence of infections. Recently, new families of lipid-derived mediators, “specialized proresolving mediators” (SPMs), were identified. SPMs play a critical role in the active resolution of inflammation by counterregulating proinflammatory signaling and promoting resolution pathways. We have identified dysregulated concentrations of lipid mediators in exhaled breath condensate, bronchoalveolar lavage fluid, and serum from patients with chronic obstructive pulmonary disease (COPD). In human alveolar macrophages from COPD and non-COPD patients, D-series resolvins decreased inflammatory cytokines and enhanced phagocytosis. To further investigate the actions of resolvins on human cells, macrophages were differentiated from human blood monocytes and treated with D-series resolvins and then exposed to cigarette smoke extract. Resolvins significantly suppressed macrophage production of proinflammatory cytokines, enzymes, and lipid mediators. Resolvins also increased anti-inflammatory cytokines, promoted an M2 macrophage phenotype, and restored cigarette smoke-induced defects in phagocytosis, highlighting the proresolving functions of these molecules. These actions were receptor-dependent and involved modulation of canonical and noncanonical NF-κB expression, with the first evidence for SPM action on alternative NF-κB signaling. These data show that resolvins act on human macrophages to attenuate cigarette smoke-induced inflammatory effects through proresolving mechanisms and provide new evidence of the therapeutic potential of SPMs.

scholarly journals Matrine reduces cigarette smoke-induced airway neutrophilic inflammation by enhancing neutrophil apoptosis

2019 ◽  
Vol 133 (4) ◽  
pp. 551-564 ◽  
Author(s):  
Xuhua Yu ◽  
Huei Jiunn Seow ◽  
Hao Wang ◽  
Desiree Anthony ◽  
Steven Bozinovski ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Lung Inflammation ◽  
Therapeutic Potential ◽  
Proteolytic Enzymes ◽  
Ex Vivo ◽  
Lavage Fluid ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Neutrophilic Inflammation ◽  
Anti Inflammatory

AbstractChronic Obstructive Pulmonary Disease (COPD) is a major incurable global health burden and will become the third largest cause of death in the world by 2030. It is well established that an exaggerated inflammatory and oxidative stress response to cigarette smoke (CS) leads to, emphysema, small airway fibrosis, mucus hypersecretion, and progressive airflow limitation. Current treatments have limited efficacy in inhibiting chronic inflammation and consequently do not reverse the pathology that initiates and drives the long-term progression of disease. In particular, there are no effective therapeutics that target neutrophilic inflammation in COPD, which is known to cause tissue damage by degranulation of a suite of proteolytic enzymes including neutrophil elastase (NE). Matrine, an alkaloid compound extracted from Sophora flavescens Ait, has well known anti-inflammatory activity. Therefore, the aim of the present study was to investigate whether matrine could inhibit CS-induced lung inflammation in mice. Matrine significantly reduced CS-induced bronchoalveolar lavage fluid (BALF) neutrophilia and NE activity in mice. The reduction in BALF neutrophils in CS-exposed mice by matrine was not due to reductions in pro-neutrophil cytokines/chemokines, but rather matrine’s ability to cause apoptosis of neutrophils, which we demonstrated ex vivo. Thus, our data suggest that matrine has anti-inflammatory actions that could be of therapeutic potential in treating CS-induced lung inflammation observed in COPD.

scholarly journals BMP-7 attenuates adverse cardiac remodeling mediated through M2 macrophages in prediabetic cardiomyopathy

2014 ◽  
Vol 307 (5) ◽  
pp. H762-H772 ◽  
Author(s):  
Princess Urbina ◽  
Dinender K. Singla
Keyword(s):  
Cardiac Function ◽  
Inflammatory Cytokines ◽  
Cardiac Remodeling ◽  
Therapeutic Potential ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Citrate Buffer ◽  
Morphogenetic Protein ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

The main objective of this study was to determine whether or not monocyte infiltration occurs in the prediabetic (PD) heart and its role in PD cardiomyopathy. We hypothesized that the PD heart is significantly populated with monocytes and that bone morphogenetic protein (BMP)-7, a novel mediator of monocyte polarization, activates infiltrated monocytes into anti-inflammatory M2 macrophages, thereby inhibiting apoptosis and fibrosis and improving cardiac function. C57Bl6 mice were assigned to control, PD, or PD + BMP-7 groups. PD and PD + BMP-7 groups were administered streptozotocin (50 mg/kg), whereas control animals received sodium citrate buffer. Afterward, the PD + BMP-7 group was administered BMP-7 (200 μg/kg) for 3 days. Our data showed significantly increased infiltrated monocytes and associated pro-inflammatory cytokines, adverse cardiac remodeling, and heart dysfunction in the PD group ( P < 0.05). Interestingly, M2 macrophage differentiation and associated anti-inflammatory cytokines were enhanced and there were reduced adverse cardiac remodeling and improved cardiac function in the PD + BMP-7 group ( P < 0.05). In conclusion, our data suggest that PD cardiomyopathy is associated with increased monocyte infiltration and released proinflammatory cytokines, which contributes to adverse cardiac remodeling and cardiac dysfunction. Moreover, we report that BMP-7 possesses novel therapeutic potential in its ability to differentiate monocytes into M2 macrophages and confer cardiac protection in the PD heart.

scholarly journals A transcriptomics-guided drug target discovery strategy identifies novel receptor ligands for lung regeneration

2021 ◽  
Author(s):  
Xinhui Wu ◽  
Sophie Bos ◽  
Thomas M Conlon ◽  
Meshal Ansari ◽  
Vicky Verschut ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Drug Target ◽  
Therapeutic Potential ◽  
Chronic Obstructive ◽  
Sequencing Analysis ◽  
Receptor Ligands ◽  
Drug Target Discovery ◽  
Target Discovery ◽  
Alveolar Epithelial

Currently, there is no pharmacological treatment targeting defective tissue repair in chronic disease. Here we utilized a transcriptomics-guided drug target discovery strategy using gene signatures of smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke, identifying druggable targets expressed in alveolar epithelial progenitors of which we screened the function in lung organoids. We found several drug targets with regenerative potential of which EP and IP prostanoid receptor ligands had the most significant therapeutic potential in restoring cigarette smoke-induced defects in alveolar epithelial progenitors in vitro and in vivo. Mechanistically, we discovered by using scRNA-sequencing analysis that circadian clock and cell cycle/apoptosis signaling pathways were enriched in alveolar epithelial progenitor cells in COPD patients and in a relevant model of COPD, which was prevented by PGE2 or PGI2 mimetics. Conclusively, specific targeting of EP and IP receptors offers therapeutic potential for injury to repair in COPD.

scholarly journals A Review of Macrophage MicroRNAs’ Role in Human Asthma

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 420 ◽  
Author(s):  
Gavriela Feketea ◽  
Corina I Bocsan ◽  
Cristian Popescu ◽  
Mihaela Gaman ◽  
Luminita A Stanciu ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Critical Role ◽  
Human Macrophage ◽  
Published Data ◽  
M2 Macrophage ◽  
Macrophage Phenotype ◽  
Activated Macrophages ◽  
Novel Therapy ◽  
Alternatively Activated Macrophages ◽  
Classically Activated Macrophages

There is an imbalance in asthma between classically activated macrophages (M1 cells) and alternatively activated macrophages (M2 cells) in favor of the latter. MicroRNAs (miRNAs) play a critical role in regulating macrophage proliferation and differentiation and control the balance of M1 and M2 macrophage polarization, thereby controlling immune responses. Here we review the current published data concerning miRNAs with known correlation to a specific human macrophage phenotype and polarization, and their association with adult asthma. MiRNA-targeted therapy is still in the initial stages, but clinical trials are under recruitment or currently running for some miRNAs in other diseases. Regulating miRNA expression via their upregulation or downregulation could show potential as a novel therapy for improving treatment efficacy in asthma.

scholarly journals Erythromycin suppresses neutrophil extracellular traps in smoking-related chronic pulmonary inflammation

2019 ◽  
Vol 10 (9) ◽  
Author(s):  
Hui Zhang ◽  
Shi-Lin Qiu ◽  
Qi-Ya Tang ◽  
Xiu Zhou ◽  
Jian-Quan Zhang ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Cigarette Smoke ◽  
Critical Role ◽  
Neutrophil Extracellular Traps ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Myeloid Dendritic Cells ◽  
Extracellular Traps

Abstract Neutrophil extracellular traps (NETs) may play a critical role in smoking-related chronic airway inflammation. However, the mechanism by which NETs induced by cigarette smoke initiate the adaptive immunity in chronic obstructive pulmonary disease (COPD) is not fully understood. In this study, we explored the effects of NETs induced by cigarette smoke on the myeloid dendritic cells (mDCs) and Th1 and Th17 cells. Additionally, we observed the inhibitory effect of erythromycin on NETs induced by cigarette smoke. We found that elevated NET levels in the sputum of COPD patients were correlated with the circulating Th1 response, mDC activation and airflow limitation. NETs induced by cigarette smoke extract (CSE) could activate monocyte-derived mDCs and promote Th1 and Th17 differentiation in vitro. Erythromycin effectively inhibited NET formation induced by CSE. In vivo, erythromycin decreased NETs in the airway and ameliorated emphysema with Th1 and Th17 cell down-regulation and CD40+ and CD86+ mDCs suppression in mice chronically exposed to cigarette smoke. These findings provide direct evidence that NETs promote the differentiation of Th1 and Th17 and play a role in the adaptive immunity of smoking-related chronic lung inflammation. Erythromycin is a potential therapeutic strategy for NETs inhibition in COPD.

scholarly journals Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages

PLoS ONE ◽  
2016 ◽  
Vol 11 (11) ◽  
pp. e0166433 ◽  
Author(s):  
Stefano Soldano ◽  
Carmen Pizzorni ◽  
Sabrina Paolino ◽  
Amelia Chiara Trombetta ◽  
Paola Montagna ◽  
...  
Keyword(s):  
M2 Macrophage ◽  
Macrophage Phenotype ◽  
Human Macrophages ◽  
Endothelin 1 ◽  
Alternatively Activated

scholarly journals Self-DNA release and STING-dependent sensing drives inflammation to cigarette smoke in mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mégane Nascimento ◽  
Aurélie Gombault ◽  
Norinne Lacerda-Queiroz ◽  
Corinne Panek ◽  
Florence Savigny ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Type I Interferon ◽  
Critical Role ◽  
Cigarette Smoke Exposure ◽  
Chronic Obstructive ◽  
Type I ◽  
Obstructive Pulmonary Disease ◽  
Interferon Pathway ◽  
Dna Release

Abstract Cigarette smoke exposure is a leading cause of chronic obstructive pulmonary disease (COPD), a major health issue characterized by airway inflammation with fibrosis and emphysema. Here we demonstrate that acute exposure to cigarette smoke causes respiratory barrier damage with the release of self-dsDNA in mice. This triggers the DNA sensor cGAS (cyclic GMP-AMP synthase) and stimulator of interferon genes (STING), driving type I interferon (IFN I) dependent lung inflammation, which are attenuated in cGAS, STING or type I interferon receptor (IFNAR) deficient mice. Therefore, we demonstrate a critical role of self-dsDNA release and of the cGAS-STING-type I interferon pathway upon cigarette smoke-induced damage, which may lead to therapeutic targets in COPD.

scholarly journals Experimental Evidence ofω-3 Polyunsaturated Fatty Acid Modulation of Inflammatory Cytokines and Bioactive Lipid Mediators: Their Potential Role in Inflammatory, Neurodegenerative, and Neoplastic Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Gabriella Calviello ◽  
Hui-Min Su ◽  
Karsten H. Weylandt ◽  
Elena Fasano ◽  
Simona Serini ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Potential Role ◽  
Current Knowledge ◽  
Critical Role ◽  
Large Body ◽  
Lipid Mediators ◽  
Neoplastic Diseases ◽  
Beneficial Effects ◽  
The Past ◽  
Inflammatory Action

A large body of evidence has emerged over the past years to show the critical role played by inflammation in the pathogenesis of several diseases including some cardiovascular, neoplastic, and neurodegenerative diseases, previously not considered inflammation-related. The anti-inflammatory action ofω-3 polyunsaturated fatty acids (PUFAs), as well as their potential healthy effects against the development and progression of the same diseases, has been widely studied by our and others’ laboratories. As a result, a rethinking is taking place on the possible mechanisms underlying the beneficial effects ofω-3 PUFAs against these disorders, and, in particular, on the influence that they may exert on the molecular pathways involved in inflammatory process, including the production of inflammatory cytokines and lipid mediators active in the resolving phase of inflammation. In the present review we will summarize and discuss the current knowledge regarding the modulating effects ofω-3 PUFAs on the production of inflammatory cytokines and proresolving or protective lipid mediators in the context of inflammatory, metabolic, neurodegenerative, and neoplastic diseases.

Sign in / Sign up

Export Citation Format

Share Document