scholarly journals The Role of Toll-Like Receptors in the Production of Cytokines by Human Lung Macrophages

2018 ◽  
Vol 12 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Stanislas Grassin-Delyle ◽  
Charlotte Abrial ◽  
Hélène Salvator ◽  
Marion Brollo ◽  
Emmanuel Naline ◽  
...  
Keyword(s):  
Human Lung ◽  
Macrophage Phenotype ◽  
Chemokine Production ◽  
Lung Macrophages ◽  
Cytokines And Chemokines ◽  
M1 Macrophage ◽  
Microbial Infections ◽  
Selective Agonists ◽  
And Function ◽  
Subtype Selective

Background: The Toll-like receptor (TLR) family is involved in the recognition of and response to microbial infections. These receptors are expressed in leukocytes. TLR stimulation induces the production of proinflammatory cytokines and chemokines. Given that human lung macrophages (LMs) constitute the first line of defense against inhaled pathogens, the objective of this study was to investigate the expression and function of TLR subtypes in this cell population. Methods: Human primary LMs were obtained from patients undergoing surgical resection. The RNA and protein expression levels of TLRs, chemokines, and cytokines were assessed after incubation with subtype-selective agonists. Results: In human LMs, the TLR expression level varied from one subtype to another. Stimulation with subtype-selective agonists induced an intense, concentration- and time-dependent increase in the production of chemokines and cytokines. TLR4 stimulation induced the strongest effect, whereas TLR9 stimulation induced a much weaker response. Conclusions: The stimulation of TLRs in human LMs induces intense cytokine and chemokine production, a characteristic of the proinflammatory M1 macrophage phenotype.

scholarly journals Signaling events involved in cytokine and chemokine production induced by secretory phospholipase A2 in human lung macrophages

2006 ◽  
Vol 36 (7) ◽  
pp. 1938-1950 ◽  
Author(s):  
Francescopaolo Granata ◽  
Annunziata Frattini ◽  
Stefania Loffredo ◽  
Annalisa Del Prete ◽  
Silvano Sozzani ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Human Lung ◽  
Secretory Phospholipase A2 ◽  
Chemokine Production ◽  
Secretory Phospholipase ◽  
Lung Macrophages ◽  
Signaling Events

scholarly journals A Novel Peptide Oligomer of Bacitracin Induces M1 Macrophage Polarization by Facilitating Ca2+ Influx

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1603
Author(s):  
Seon Yeong Ji ◽  
Hyesook Lee ◽  
Hyun Hwangbo ◽  
Su-Hyun Hong ◽  
Hee-Jae Cha ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Inflammatory Mediators ◽  
Macrophage Polarization ◽  
Mitogen Activated Protein Kinase ◽  
Raw 264.7 Cells ◽  
Macrophage Phenotype ◽  
Cytokines And Chemokines ◽  
M1 Macrophage ◽  
Bacillus Spp

Antimicrobial peptides (AMPs) are components of the innate immune system and form the first defense against pathogens for various organisms. In the present study, we assessed whether CSP32, a novel AMP oligomer of bacitracin isolated from a strain of Bacillus spp., regulates the polarization of murine macrophage-like RAW 264.7 cells. CSP32 stimulated phagocytosis while inducing the appearance of the typical M1 polarized macrophage phenotype; these M1 macrophages play a role in host defense against pathogens. Furthermore, our results showed that CSP32 enhanced the expression and production of pro-inflammatory mediators, such as cytokines and chemokines. In addition, the CSP32-stimulated inflammatory mediators were induced mainly by the mitogen-activated protein kinase/nuclear factor kappa B (MAPK/NF-κB) signaling pathway during M1 macrophage polarization. In particular, CSP32 markedly increased the numbers of Ca2+-positive macrophages while upregulating phospholipase C and activating protein kinase Cε. Furthermore, the inhibition of intracellular Ca2+ by BAPTA-AM, a Ca2+ chelator, significantly suppressed the CSP32-mediated phagocytosis, inflammatory mediator production, and NF-κB activation. In conclusion, our data suggested that CSP32-stimulated M1 macrophage polarization is dependent on the calcium signaling pathway and may result in enhanced immune capacities.

scholarly journals Effects of corticosteroids on COPD lung macrophage phenotype and function

2020 ◽  
Vol 134 (7) ◽  
pp. 751-763 ◽  
Author(s):  
Andrew Higham ◽  
Tom Scott ◽  
Jian Li ◽  
Rosemary Gaskell ◽  
Aisha Baba Dikwa ◽  
...  
Keyword(s):  
Inhaled Corticosteroids ◽  
Corticosteroid Treatment ◽  
Therapeutic Benefit ◽  
Chronic Obstructive ◽  
Macrophage Phenotype ◽  
Lung Macrophages ◽  
Lung Macrophage ◽  
Copd Patients ◽  
Gene And Protein Expression ◽  
And Function

Abstract The numbers of macrophages are increased in the lungs of chronic obstructive pulmonary disease (COPD) patients. COPD lung macrophages have reduced ability to phagocytose microbes and efferocytose apoptotic cells. Inhaled corticosteroids (ICSs) are widely used anti-inflammatory drugs in COPD; however, their role beyond suppression of cytokine release has not been explored in COPD macrophages. We have examined the effects of corticosteroids on COPD lung macrophage phenotype and function. Lung macrophages from controls and COPD patients were treated with corticosteroids; effects on gene and protein expression of CD163, CD164, CD206, MERTK, CD64, CD80 and CD86 were studied. We also examined the effect of corticosteroids on the function of CD163, MERTK and cluster of differentiation 64 (CD64). Corticosteroid increased CD163, CD164, CD206 and MERTK expression and reduced CD64, CD80 and CD86 expression. We also observed an increase in the uptake of the haemoglobin–haptoglobin complex (CD163) from 59 up to 81% and an increase in efferocytosis of apoptotic neutrophils (MERTK) from 15 up to 28% following corticosteroid treatment. We observed no effect on bacterial phagocytosis. Corticosteroids alter the phenotype and function of COPD lung macrophages. Our findings suggest mechanisms by which corticosteroids exert therapeutic benefit in COPD, reducing iron available for bacterial growth and enhancing efferocytosis.

Reprogrammed M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 extends lifespan of mice with experimental carcinoma

2017 ◽  
pp. 4-9
Author(s):  
С.В. Калиш ◽  
С.В. Лямина ◽  
А.А. Раецкая ◽  
И.Ю. Малышев
Keyword(s):  
Tumor Growth ◽  
Culture Medium ◽  
Ehrlich Carcinoma ◽  
Macrophage Phenotype ◽  
M1 Macrophages ◽  
M1 Macrophage ◽  
Ec Cells ◽  
Experimental Carcinoma

Цель исследования. Репрограммирование М1 фенотипа макрофагов с ингибированными факторами транскрипции М2 фенотипа STAT3, STAТ6 и SMAD и оценка их влияния на развитие карциномы Эрлиха (КЭ) in vitro и in vivo. Методика. Рост опухоли иницировали in vitro путем добавления клеток КЭ в среду культивирования RPMI-1640 и in vivo путем внутрибрюшинной инъекции клеток КЭ мышам. Результаты. Установлено, что M1макрофаги и in vitro, и in vivo оказывают выраженный противоопухолевый эффект, который превосходит антиопухолевые эффекты М1, M1, M1 макрофагов и цисплатина. Заключение. М1 макрофаги с ингибированными STAT3, STAT6 и/или SMAD3 эффективно ограничивают рост опухоли. Полученные данные обосновывают разработку новой технологии противоопухолевой клеточной терапии. Objective. Reprogramming of M1 macrophage phenotype with inhibited M2 phenotype transcription factors, such as STAT3, STAT6 and SMAD and assess their impact on the development of Ehrlich carcinoma (EC) in vitro and in vivo . Methods. Tumor growth in vitro was initiated by addition of EC cells in RPMI-1640 culture medium and in vivo by intraperitoneal of EC cell injection into mice. Results. It was found that M1 macrophages have a pronounced anti-tumor effect in vitro , and in vivo , which was greater than anti-tumor effects of M1, M1, M1 macrophages and cisplatin. Conclusion. M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 effectively restrict tumor growth. The findings justify the development of new anti-tumor cell therapy technology.

scholarly journals Modulation of Innate Immune Toxicity by Silver Nanoparticle Exposure and the Preventive Effects of Pterostilbene

2021 ◽  
Vol 22 (5) ◽  
pp. 2536
Author(s):  
Rong-Jane Chen ◽  
Chiao-Ching Huang ◽  
Rosita Pranata ◽  
Yu-Hsuan Lee ◽  
Yu-Ying Chen ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Good Alternative ◽  
Innate Immune ◽  
Toxic Effects ◽  
Transgenic Zebrafish ◽  
Zebrafish Model ◽  
Cytokines And Chemokines ◽  
Living Organisms ◽  
And Function ◽  
Immune Toxicity

Silver nanoparticles pose a potential risk to ecosystems and living organisms due to their widespread use in various fields and subsequent gradual release into the environment. Only a few studies have investigated the effects of silver nanoparticles (AgNPs) toxicity on immunological functions. Furthermore, these toxic effects have not been fully explored. Recent studies have indicated that zebrafish are considered a good alternative model for testing toxicity and for evaluating immunological toxicity. Therefore, the purpose of this study was to investigate the toxicity effects of AgNPs on innate immunity using a zebrafish model and to investigate whether the natural compound pterostilbene (PTE) could provide protection against AgNPs-induced immunotoxicity. Wild type and neutrophil- and macrophage-transgenic zebrafish lines were used in the experiments. The results indicated that the exposure to AgNPs induced toxic effects including death, malformation and the innate immune toxicity of zebrafish. In addition, AgNPs affect the number and function of neutrophils and macrophages. The expression of immune-related cytokines and chemokines was also affected. Notably, the addition of PTE could activate immune cells and promote their accumulation in injured areas in zebrafish, thereby reducing the damage caused by AgNPs. In conclusion, AgNPs may induce innate immune toxicity and PTE could ameliorate this toxicity.

scholarly journals Macrophage Phenotype and Function in Different Stages of Atherosclerosis

2016 ◽  
Vol 118 (4) ◽  
pp. 653-667 ◽  
Author(s):  
Ira Tabas ◽  
Karin E. Bornfeldt
Keyword(s):  
Macrophage Phenotype ◽  
And Function

scholarly journals Thioester-Containing Protein-4 Regulates the Drosophila Immune Signaling and Function against the Pathogen Photorhabdus

2016 ◽  
Vol 9 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Upasana Shokal ◽  
Ioannis Eleftherianos
Keyword(s):  
Immune Response ◽  
Photorhabdus Luminescens ◽  
Human Pathogen ◽  
Loss Of Function ◽  
Phenoloxidase Activity ◽  
Microbial Infections ◽  
Immune Pathways ◽  
And Function ◽  
Important Progress

Despite important progress in identifying the molecules that participate in the immune response of Drosophila melanogaster to microbial infections, the involvement of thioester-containing proteins (TEPs) in the antibacterial immunity of the fly is not fully clarified. Previous studies mostly focused on identifying the function of TEP2, TEP3 and TEP6 molecules in the D. melanogaster immune system. Here, we investigated the role of TEP4 in the regulation and function of D. melanogaster host defense against 2 virulent pathogens from the genus Photorhabdus, i.e. the insect pathogenic bacterium Photorhabdus luminescens and the emerging human pathogen P. asymbiotica. We demonstrate that Tep4 is strongly upregulated in adult flies following the injection of Photorhabdus bacteria. We also show that Tep4 loss-of-function mutants are resistant to P. luminescens but not to P. asymbiotica infection. In addition, we find that inactivation of Tep4 results in the upregulation of the Toll and Imd immune pathways, and the downregulation of the Jak/Stat and Jnk pathways upon Photorhabdus infection. We document that loss of Tep4 promotes melanization and phenoloxidase activity in the mutant flies infected with Photorhabdus. Together, these findings generate novel insights into the immune role of TEP4 as a regulator and effector of the D. melanogaster antibacterial immune response.

Regulation of human lung fibroblast phenotype and function by vitronectin and vitronectin integrins

2001 ◽  
Vol 114 (19) ◽  
pp. 3507-3516 ◽  
Author(s):  
Amelia K. Scaffidi ◽  
Yuben P. Moodley ◽  
Markus Weichselbaum ◽  
Philip J. Thompson ◽  
Darryl A. Knight
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Monoclonal Antibodies ◽  
Human Lung ◽  
Stress Fibers ◽  
Collagen Gels ◽  
Human Lung Fibroblast ◽  
Myofibroblast Phenotype ◽  
And Function ◽  
Blocking Antibodies

Myofibroblasts, characterised by high expression of α-smooth muscle actin (α-SMA), are important and transient cells in normal wound healing but are found in increased number in various pathological conditions of the lung including asthma and pulmonary fibrosis. The mechanisms that regulate the myofibroblast phenotype are unknown but are likely to involve signals from the extracellular matrix transmitted via specific integrins. Vitronectin is a glycoprotein released during inflammation and has been shown to regulate the phenotype of vascular smooth muscle cells via αv and β1 integrins. In the current study we have examined whether vitronectin influences the phenotype and function of normal human lung fibroblasts (HFL-1). Incubation of HFL-1 cells with vitronectin induced a concentration-dependent reduction in α-SMA expression. By contrast, function-blocking monoclonal antibodies to the vitronectin integrins αv, β1, αvβ3 and αvβ5 induced the expression of α-SMA and its organization into stress fibers. Expression of α-SMA induced by all function-blocking monoclonal antibodies was abrogated by inhibition of protein kinase C and phosphatidylinositol-3 kinase, but the effects of inhibition of other signalling pathways was integrin dependent. Exposure to other extracellular matrix proteins such as fibronectin, collagen or their integrins did not influence expression of α-SMA. The expression and organization of α-SMA induced by exposure to function-blocking antibodies was translated into an augmented capacity of HFL-1 cells to contract fibroblast populated collagen gels. By contrast, contraction of collagen gels following incubation with vitronectin was not significantly different to control. This study has shown that vitronectin influences the phenotype and behaviour of HFL-1 cells by downregulating the expression of α-SMA and reducing their contractile ability. By contrast, occupancy of specific integrins by function-blocking antibodies upregulated the expression of α-SMA and induced the formation of functional stress fibers capable of contracting collagen gels. These results suggest that vitronectin modulates the fibroblast-myofibroblast phenotype, implying an important role in the remodelling process during lung development or response to injury.

Abstract 190: Epigenetic Modifications of Pro-inflammatory Gene Expression in Macrophages by a Demethylase Enzyme, JMJD3, May Promote Chronic Inflammation in Type 2 Diabetic (T2D) Wounds

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Katherine A Gallagher ◽  
Amrita Joshi ◽  
William Carson ◽  
Dawn Coleman ◽  
Peter Henke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Chronic Inflammation ◽  
Histone Methylation ◽  
Gene Promoter ◽  
Epigenetic Modifications ◽  
Macrophage Phenotype ◽  
M1 Macrophage ◽  
Type 2 Diabetic

Introduction Type 2 diabetic(T2D) wounds are characterized by chronic inflammation, maintained by an exaggerated M1(pro-inflammatory) macrophage phenotype response. We seek to define a link between epigenetic modifications of bone marrow(BM) cells in T2D and dysregulated macrophages in wounds. We hypothesized that a chromatin modifying demethylase enzyme, JMJD3, is responsible for the decrease in H3K27me3 repressive methylation at the IL-12 gene promoter and thus drives an M1 macrophage phenotype in T2D wounds. Methods BM/adipose tissue(AT)/wounds were harvested from 30 diet-induced obese mice(DIO)(MG= 350g/DL) and 30 matched(WT) controls. For chromatin immunoprecipitation(ChIP) analysis, cells were isolated via ferromagnetic columns(CD34+,CD11b+). ChIP to detect histone methylation at the promoter regions of JMJD3 and IL-12(key M1 macrophage gene) was performed and RNA analysis was done with standard primers. Results JMJD3 mRNA in the BM is significantly increased in the DIO versus WT. ChIP showed increased H3K4me3(gene expression mark) in CD34+ progenitor cells and a corresponding decrease in H3K27me3(repressive mark) in monocytes at the promoter region of JMJD3. These changes correspond with the decrease in H3K27me3 seen at the IL-12 promoter in macrophages(CD11b+) from AT/T2D wounds. Conclusions Epigenetic changes initiated by JMJD3 in BM progenitor cells result in changes in histone methylation at the IL-12 promoter favoring an M1 phenotype in macrophages and thus contributes to the chronic inflammation seen in T2D wounds and AT. Whether manipulation of epigenetic enzymes could reduce chronic inflammation in T2D wounds requires further work.

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