scholarly journals Myeloperoxidase Modulates Hydrogen Peroxide Mediated Cellular Damage in Murine Macrophages

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1255
Author(s):  
Chaorui Guo ◽  
Inga Sileikaite ◽  
Michael J. Davies ◽  
Clare L. Hawkins
Keyword(s):  
Hydrogen Peroxide ◽  
Hypochlorous Acid ◽  
Cell Function ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Cellular Damage ◽  
Enzymatic System ◽  
Therapeutic Approaches ◽  
Macrophage Cell

Myeloperoxidase (MPO) is involved in the development of many chronic inflammatory diseases, in addition to its key role in innate immune defenses. This is attributed to the excessive production of hypochlorous acid (HOCl) by MPO at inflammatory sites, which causes tissue damage. This has sparked wide interest in the development of therapeutic approaches to prevent HOCl-induced cellular damage including supplementation with thiocyanate (SCN−) as an alternative substrate for MPO. In this study, we used an enzymatic system composed of glucose oxidase (GO), glucose, and MPO in the absence and presence of SCN−, to investigate the effects of generating a continuous flux of oxidants on macrophage cell function. Our studies show the generation of hydrogen peroxide (H2O2) by glucose and GO results in a dose- and time-dependent decrease in metabolic activity and cell viability, and the activation of stress-related signaling pathways. Interestingly, these damaging effects were attenuated by the addition of MPO to form HOCl. Supplementation with SCN−, which favors the formation of hypothiocyanous acid, could reverse this effect. Addition of MPO also resulted in upregulation of the antioxidant gene, NAD(P)H:quinone acceptor oxidoreductase 1. This study provides new insights into the role of MPO in the modulation of macrophage function, which may be relevant to inflammatory pathologies.

scholarly journals The Role of Extracellular Vesicles in Cutaneous Remodeling and Hair Follicle Dynamics

2019 ◽  
Vol 20 (11) ◽  
pp. 2758 ◽  
Author(s):  
Elisa Carrasco ◽  
Gonzalo Soto-Heredero ◽  
María Mittelbrunn
Keyword(s):  
Hair Follicle ◽  
Extracellular Vesicles ◽  
Cell Function ◽  
Hair Follicles ◽  
The Body ◽  
Epithelial Stem Cells ◽  
Therapeutic Approaches ◽  
Waste Products ◽  
Efficient Treatment

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are cell-derived membranous structures that were originally catalogued as a way of releasing cellular waste products. Since the discovery of their function in intercellular communication as carriers of proteins, lipids, and DNA and RNA molecules, numerous therapeutic approaches have focused on the use of EVs, in part because of their minimized risk compared to cell-based therapies. The skin is the organ with the largest surface in the body. Besides the importance of its body barrier function, much attention has been paid to the skin in regenerative medicine because of its cosmetic aspect, which is closely related to disorders affecting pigmentation and the presence or absence of hair follicles. The use of exosomes in therapeutic approaches for cutaneous wound healing has been reported and is briefly reviewed here. However, less attention has been paid to emerging interest in the potential capacity of EVs as modulators of hair follicle dynamics. Hair follicles are skin appendices that mainly comprise an epidermal and a mesenchymal component, with the former including a major reservoir of epithelial stem cells but also melanocytes and other cell types. Hair follicles continuously cycle, undergoing consecutive phases of resting, growing, and regression. Many biomolecules carried by EVs have been involved in the control of the hair follicle cycle and stem cell function. Thus, investigating the role of either naturally produced or therapeutically delivered EVs as signaling vehicles potentially involved in skin homeostasis and hair cycling may be an important step in the attempt to design future strategies towards the efficient treatment of several skin disorders.

scholarly journals Autophagy Intertwines with Different Diseases—Recent Strategies for Therapeutic Approaches

Diseases ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 15 ◽  
Author(s):  
Janani Ramesh ◽  
Larance Ronsard ◽  
Anthony Gao ◽  
Bhuvarahamurthy Venugopal
Keyword(s):  
Inflammatory Diseases ◽  
Therapeutic Strategies ◽  
Open Reading Frames ◽  
Signaling Cascades ◽  
Progression Rate ◽  
Therapeutic Approaches ◽  
Genes Encoding ◽  
Novel Therapeutic Strategies ◽  
Reading Frames

Autophagy is a regular and substantial “clear-out process” that occurs within the cell and that gets rid of debris that accumulates in membrane-enclosed vacuoles by using enzyme-rich lysosomes, which are filled with acids that degrade the contents of the vacuoles. This machinery is well-connected with many prevalent diseases, including cancer, HIV, and Parkinson’s disease. Considering that autophagy is well-known for its significant connections with a number of well-known fatal diseases, a thorough knowledge of the current findings in the field is essential in developing therapies to control the progression rate of diseases. Thus, this review summarizes the critical events comprising autophagy in the cellular system and the significance of its key molecules in manifesting this pathway in various diseases for down- or upregulation. We collectively reviewed the role of autophagy in various diseases, mainly neurodegenerative diseases, cancer, inflammatory diseases, and renal disorders. Here, some collective reports on autophagy showed that this process might serve as a dual performer: either protector or contributor to certain diseases. The aim of this review is to help researchers to understand the role of autophagy-regulating genes encoding functional open reading frames (ORFs) and its connection with diseases, which will eventually drive better understanding of both the progression and suppression of different diseases at various stages. This review also focuses on certain novel therapeutic strategies which have been published in the recent years based on targeting autophagy key proteins and its interconnecting signaling cascades.

scholarly journals Microbiota in Healthy Skin and in Atopic Eczema

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Giuseppe Baviera ◽  
Maria Chiara Leoni ◽  
Lucetta Capra ◽  
Francesca Cipriani ◽  
Giorgio Longo ◽  
...  
Keyword(s):  
Atopic Eczema ◽  
Inflammatory Diseases ◽  
Normal Skin ◽  
Innate Immune ◽  
Microbiota Composition ◽  
Healthy Skin ◽  
Skin Microbiota ◽  
Disease States ◽  
The Relationship

The Italian interest group (IG) on atopic eczema and urticaria is member of the Italian Society of Allergology and Immunology. The aim of our IG is to provide a platform for scientists, clinicians, and experts. In this review we discuss the role of skin microbiota not only in healthy skin but also in skin suffering from atopic dermatitis (AD). A Medline and Embase search was conducted for studies evaluating the role of skin microbiota. We examine microbiota composition and its development within days after birth; we describe the role of specific groups of microorganisms that colonize distinct anatomical niches and the biology and clinical relevance of antimicrobial peptides expressed in the skin. Specific AD disease states are characterized by concurrent and anticorrelated shifts in microbial diversity and proportion ofStaphylococcus. These organisms may protect the host, defining them not as simple symbiotic microbes but rather as mutualistic microbes. These findings reveal links between microbial communities and inflammatory diseases such as AD and provide novel insights into global shifts of bacteria relevant to disease progression and treatment. This review also highlights recent observations on the importance of innate immune systems and the relationship with normal skin microflora for the maintenance of healthy skin.

scholarly journals Deciphering the Intracellular Fate ofPropionibacterium acnesin Macrophages

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Natalie Fischer ◽  
Tim N. Mak ◽  
Debika Biswal Shinohara ◽  
Karen S. Sfanos ◽  
Thomas F. Meyer ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Opportunistic Pathogen ◽  
Human Macrophage ◽  
Macrophage Cell ◽  
Common Skin ◽  
Ph Neutralization ◽  
Prostatic Inflammation ◽  
Skin Bacterium ◽  
Intracellular Fate

Propionibacterium acnesis a Gram-positive bacterium that colonizes various niches of the human body, particularly the sebaceous follicles of the skin. Over the last years a role of this common skin bacterium as an opportunistic pathogen has been explored. Persistence ofP. acnesin host tissue has been associated with chronic inflammation and disease development, for example, in prostate pathologies. This study investigated the intracellular fate ofP. acnesin macrophages after phagocytosis. In a mouse model ofP. acnes-induced chronic prostatic inflammation, the bacterium could be detected in prostate-infiltrating macrophages at 2 weeks postinfection. Further studies performed in the human macrophage cell line THP-1 revealed intracellular survival and persistence ofP. acnesbut no intracellular replication or escape from the host cell. Confocal analyses of phagosome acidification and maturation were performed. Acidification ofP. acnes-containing phagosomes was observed at 6 h postinfection but then lost again, indicative of cytosolic escape ofP. acnesor intraphagosomal pH neutralization. No colocalization with the lysosomal markers LAMP1 and cathepsin D was observed, implying that theP. acnes-containing phagosome does not fuse with lysosomes. Our findings give first insights into the intracellular fate ofP. acnes; its persistency is likely to be important for the development ofP. acnes-associated inflammatory diseases.

scholarly journals New Insights on the Role of pentraxin-3 in Allergic Asthma

2021 ◽  
Vol 2 ◽  
Author(s):  
Latifa Koussih ◽  
Samira Atoui ◽  
Omar Tliba ◽  
Abdelilah S. Gounni
Keyword(s):  
Immune Response ◽  
Allergic Asthma ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Protective Role ◽  
Severe Form ◽  
Innate Immune ◽  
Pentraxin 3 ◽  
Complement Components

Pentraxins are soluble pattern recognition receptors that play a major role in regulating innate immune responses. Through their interaction with complement components, Fcγ receptors, and different microbial moieties, Pentraxins cause an amplification of the inflammatory response. Pentraxin-3 is of particular interest since it was identified as a biomarker for several immune-pathological diseases. In allergic asthma, pentraxin-3 is produced by immune and structural cells and is up-regulated by pro-asthmatic cytokines such as TNFα and IL-1β. Strikingly, some recent experimental evidence demonstrated a protective role of pentraxin-3 in chronic airway inflammatory diseases such as allergic asthma. Indeed, reduced pentraxin-3 levels have been associated with neutrophilic inflammation, Th17 immune response, insensitivity to standard therapeutics and a severe form of the disease. In this review, we will summarize the current knowledge of the role of pentraxin-3 in innate immune response and discuss the protective role of pentraxin-3 in allergic asthma.

The Role of Autophagy in Hydrogen Peroxide‐ or Methylglyoxal‐induced Cellular Damage in H9c2 Cells

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Amogh Sehgal ◽  
Halil Onal ◽  
Rose Martorana ◽  
Catherine Wastella ◽  
Adona Pjetergjoka ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Cellular Damage ◽  
H9c2 Cells

scholarly journals The Role of gp130 Cytokines in Tuberculosis

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2695
Author(s):  
Kristina Ritter ◽  
Jasmin Rousseau ◽  
Christoph Hölscher
Keyword(s):  
Inflammatory Diseases ◽  
Therapeutic Approaches ◽  
Duration Of Treatment ◽  
Common Receptor ◽  
Promising Target ◽  
Increased Risk ◽  
The Common ◽  
Combine Administration ◽  
Cytokine Networks

Protective immune responses to Mycobacterium tuberculosis (Mtb) infection substantially depend on a delicate balance within cytokine networks. Thus, immunosuppressive therapy by cytokine blockers, as successfully used in the management of various chronic inflammatory diseases, is often connected with an increased risk for tuberculosis (TB) reactivation. Hence, identification of alternative therapeutics which allow the treatment of inflammatory diseases without compromising anti-mycobacterial immunity remains an important issue. On the other hand, in the context of novel therapeutic approaches for the management of TB, host-directed adjunct therapies, which combine administration of antibiotics with immunomodulatory drugs, play an increasingly important role, particularly to reduce the duration of treatment. In both respects, cytokines/cytokine receptors related to the common receptor subunit gp130 may serve as promising target candidates. Within the gp130 cytokine family, interleukin (IL)-6, IL-11 and IL-27 are most explored in the context of TB. This review summarizes the differential roles of these cytokines in protection and immunopathology during Mtb infection and discusses potential therapeutic implementations with respect to the aforementioned approaches.

scholarly journals Mitochondrial DNA: A Key Regulator of Anti-Microbial Innate Immunity

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 86 ◽  
Author(s):  
Saima Kausar ◽  
Liqun Yang ◽  
Muhammad Nadeem Abbas ◽  
Xin Hu ◽  
Yongju Zhao ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Mitochondrial Dna ◽  
Signaling Pathways ◽  
Inflammatory Diseases ◽  
Cpg Islands ◽  
Innate Immune ◽  
Cellular Damage ◽  
Immune Signaling ◽  
Molecular Pattern ◽  
Characteristic Features

During the last few years, mitochondrial DNA has attained much attention as a modulator of immune responses. Due to common evolutionary origin, mitochondrial DNA shares various characteristic features with DNA of bacteria, as it consists of a remarkable number of unmethylated DNA as 2′-deoxyribose cytidine-phosphate-guanosine (CpG) islands. Due to this particular feature, mitochondrial DNA seems to be recognized as a pathogen-associated molecular pattern by the innate immune system. Under the normal physiological situation, mitochondrial DNA is enclosed in the double membrane structure of mitochondria. However, upon pathological conditions, it is usually released into the cytoplasm. Growing evidence suggests that this cytosolic mitochondrial DNA induces various innate immune signaling pathways involving NLRP3, toll-like receptor 9, and stimulator of interferon genes (STING) signaling, which participate in triggering downstream cascade and stimulating to produce effector molecules. Mitochondrial DNA is responsible for inflammatory diseases after stress and cellular damage. In addition, it is also involved in the anti-viral and anti-bacterial innate immunity. Thus, instead of entire mitochondrial importance in cellular metabolism and energy production, mitochondrial DNA seems to be essential in triggering innate anti-microbial immunity. Here, we describe existing knowledge on the involvement of mitochondrial DNA in the anti-microbial immunity by modulating the various immune signaling pathways.

scholarly journals Inflammatory signaling regulates hematopoietic stem and progenitor cell development and homeostasis

2021 ◽  
Vol 218 (7) ◽  
Author(s):  
Amélie Collins ◽  
Carl A. Mitchell ◽  
Emmanuelle Passegué
Keyword(s):  
Progenitor Cell ◽  
Cell Function ◽  
Therapeutic Approaches ◽  
Inflammatory Signaling ◽  
Hematopoietic Stem ◽  
Commensal Microbiota ◽  
Stem And Progenitor Cells ◽  
Embryonic Life ◽  
Emergency Myelopoiesis

Inflammation exerts multiple effects on the early hematopoietic compartment. Best studied is the role of proinflammatory cytokines in activating adult hematopoietic stem and progenitor cells to dynamically replenish myeloid lineage cells in a process known as emergency myelopoiesis. However, it is increasingly appreciated that the same proinflammatory signaling pathways are used in diverse hematopoietic scenarios. This review focuses on inflammatory signaling in the emergence of the definitive hematopoietic compartment during embryonic life, and tonic inflammatory signals derived from commensal microbiota in shaping the adult hematopoietic compartment in the absence of pathogenic insults. Insights into the unique and shared aspects of inflammatory signaling that regulate hematopoietic stem and progenitor cell function across the lifespan and health span of an individual will enable better diagnostic and therapeutic approaches to hematopoietic dysregulation and malignancies.

Abstract 641: The Role of Interleukin-23 in the Development of Atherosclerosis

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Aliia Fatkhullina ◽  
Iuliia Peshkova ◽  
Ekaterina Koltsova
Keyword(s):  
T Cells ◽  
Cell Function ◽  
Inflammatory Diseases ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Chronic Inflammatory Disease ◽  
Lymphoid Cells ◽  
Efficient Manner ◽  
Mediators Of Inflammation

Atherosclerosis is lipid-driven chronic inflammatory disease of the arterial wall mediated by innate and adaptive immune responses. Inflammation promotes the development atherosclerotic plaques. Cytokines are soluble mediators of inflammation and important players in the pathogenesis of atherosclerosis. IL-23, a cytokine of IL-6/IL-12 cytokines superfamily is produced by myeloid cells and regulates the production of IL-17 and IL-22 by T helper IL-17 producing (Th17) cells, innate lymphoid cells of type 3 (ILC3) and gamma delta T cells in various auto-inflammatory diseases. IL-23R expression was also detected on myeloid cells but its role in regulation of myeloid cell function is not well defined. The level of IL-23 was shown to be upregulated in cardiovascular pathologies. Therefore, we decided to address the role of IL-23 in atherosclerosis using Il23p19 and Il23(R) receptor deficient mice. Surprisingly, atherosclerosis prone, Ldlr -/- mice transplanted with Il23p19 -/- or Il23r -/- bone marrow and fed with Western diet (WD) for 14 weeks demonstrated acceleration of atherosclerosis progression, which was characterized by increased accumulation of various hematopoietic cells in the aortas. Analysis of cytokine production unexpectedly revealed no changes in IL-17A and IFN-gamma production among CD4 T cells in the aortas. This effect was specific to aortas, as IL-17A production in the intestine of Il23p19 -/- mice was reduced, similarly to previously published observations. On the other hand, macrophages from Il23p19 -/- mice were able to uptake oxLDL in more efficient manner compared to wt controls, suggesting the regulatory role of IL-23 in foam cells formation. We also found enhanced inflammatory gene expression in aortas of Il23p19 -/- -> Ldlr -/- and Il23r -/- -> Ldlr -/- mice compared to wt controls. Overall our data suggest IL-17 independent atheroprotective role of IL-23.

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