scholarly journals Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases

2018 ◽  
Vol 19 (8) ◽  
pp. 2208 ◽  
Author(s):  
Yen-Chun Koh ◽  
Guliang Yang ◽  
Ching-Shu Lai ◽  
Monthana Weerawatanakorn ◽  
Min-Hsiung Pan
Keyword(s):  
Disease Progression ◽  
Metabolic Diseases ◽  
Macrophage Polarization ◽  
Colorectal Disease ◽  
New Approach ◽  
Adaptive Immune ◽  
Cytokines And Chemokines ◽  
Preventive Actions ◽  
Pro Inflammatory Cytokines

Macrophages can polarize into two different states (M1 and M2), which play contrasting roles during pathogenesis or tissue damage. M1 polarized macrophages produce pro-inflammatory cytokines and mediators resulting in inflammation, while M2 macrophages have an anti-inflammatory effect. Secretion of appropriate cytokines and chemokines from macrophages can lead to the modification of the microenvironment for bridging innate and adaptive immune responses. Increasing evidence suggests that polarized macrophages are pivotal for disease progression, and the regulation of macrophage polarization may provide a new approach in therapeutic treatment of inflammation-related diseases, including cancer, obesity and metabolic diseases, fibrosis in organs, brain damage and neuron injuries, and colorectal disease. Polarized macrophages affect the microenvironment by secreting cytokines and chemokines while cytokines or mediators that are produced by resident cells or tissues may also influence macrophages behavior. The interplay of macrophages and other cells can affect disease progression, and therefore, understanding the activation of macrophages and the interaction between polarized macrophages and disease progression is imperative prior to taking therapeutic or preventive actions. Manipulation of macrophages can be an entry point for disease improvement, but the mechanism and potential must be understood. In this review, some advanced studies regarding the role of macrophages in different diseases, potential mechanisms involved, and intervention of drugs or phytochemicals, which are effective on macrophage polarization, will be discussed.

scholarly journals The Role of the Immune System in Huntington’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Gisa Ellrichmann ◽  
Christiane Reick ◽  
Carsten Saft ◽  
Ralf A. Linker
Keyword(s):  
Immune System ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Disease Progression ◽  
Adaptive Immune System ◽  
Cag Repeats ◽  
Adaptive Immune ◽  
Adaptive Immune Systems ◽  
Migration Of Macrophages

Huntington’s disease (HD) is characterized by a progressive course of disease until death 15–20 years after the first symptoms occur and is caused by a mutation with expanded CAG repeats in the huntingtin (htt) protein. Mutant htt (mhtt) in the striatum is assumed to be the main reason for neurodegeneration. Knowledge about pathophysiology has rapidly improved discussing influences of excitotoxicity, mitochondrial damage, free radicals, and inflammatory mechanisms. Both innate and adaptive immune systems may play an important role in HD. Activation of microglia with expression of proinflammatory cytokines, impaired migration of macrophages, and deposition of complement factors in the striatum indicate an activation of the innate immune system. As part of the adaptive immune system, dendritic cells (DCs) prime T-cell responses secreting inflammatory mediators. In HD, DCs may contain mhtt which brings the adaptive immune system into the focus of interest. These data underline an increasing interest in the peripheral immune system for pathomechanisms of HD. It is still unclear if neuroinflammation is a reactive process or if there is an active influence on disease progression. Further understanding the influence of inflammation in HD using mouse models may open various avenues for promising therapeutic approaches aiming at slowing disease progression or forestalling onset of disease.

scholarly journals MicroRNA target Fc receptors to regulate Ab-dependent Ag uptake in primary macrophages and dendritic cells

2016 ◽  
Vol 22 (7) ◽  
pp. 510-521 ◽  
Author(s):  
Afsar Raza Naqvi ◽  
Jezrom B Fordham ◽  
Salvador Nares
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Innate Immune Responses ◽  
Microrna Target ◽  
Adaptive Immune ◽  
Latex Beads ◽  
Tnf Α ◽  
Particle Internalization ◽  
Pro Inflammatory Cytokines

Phagocytosis commences with particle internalization and culminates with the activation of innate and adaptive immune responses. However, the role of miRNAs in phagocytosis remains largely unknown. In this study, we examined the role of miR-24, miR-30b and miR-142-3p in Ab Fc receptor (FcR)-mediated phagocytosis by macrophages (MΦ) and dendritic cells (DC). The expression of these miRNAs was reduced following phagocytosis of both IgG-opsonized beads and Escherichia coli, indicating their regulatory role in the process. Further, overexpression of these miRNAs impaired the uptake of IgG-coated latex beads, which corroborated the reduced secretion of the pro-inflammatory cytokines TNF-α and IL-8 and down-regulation of PKC-α, as well as superoxide-generating enzyme NADPH oxidase 2 expression level. Mechanistically, MΦ and DC transfected with miRNA mimics show marked reduction in expression of FcRs including FCGR2A, FcɛR1G and FCER2. We show that FcɛR1G expression is not affected at the transcription level, rather it is post-transcriptionally regulated by miR-30b. Finally, we demonstrate that siRNA-mediated knockdown of FcɛR1G leads to reduced uptake of IgG-opsonized beads, indicating its involvement on Ab-mediated phagocytosis. These results uncover miR-24, miR-30b and miR-142-3p as an essential component of FcR-mediated phagocytosis and associated innate immune responses.

Macrophage Polarization: Implications on Metabolic Diseases and the Role of Exercise

2016 ◽  
Vol 26 (2) ◽  
pp. 115-132 ◽  
Author(s):  
Loreana Sanches Silveira ◽  
Barbara de Moura Mello Antunes ◽  
Andre Luis Araujo Minari ◽  
Ronaldo Vagner Thomatieli dos Santos ◽  
José Cesar Rosa Neto ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Macrophage Polarization

scholarly journals Anti-inflammatory Treatment and Cardiovascular Outcomes: Results of Clinical Trials

2021 ◽  
Vol 16 ◽  
Author(s):  
Alberto J Lorenzatti
Keyword(s):  
Clinical Trials ◽  
Arterial Wall ◽  
Plaque Formation ◽  
Phase Iii ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Phase Iii Clinical Trials ◽  
Cytokines And Chemokines ◽  
Pro Inflammatory Cytokines

Atherosclerosis is a chronic inflammatory disorder of the vasculature where cholesterol accumulates in the arterial wall stimulating infiltration of immune cells. This plays an important role in plaque formation, as well as complications caused by its build up. Pro-inflammatory cytokines and chemokines are implicated throughout the progression of the disease and different therapies that aim to resolve this chronic inflammation, reduce cardiovascular (CV) events and improve clinical outcomes have been tested. The results from the pivotal CANTOS trial show that targeting the pro-inflammatory cytokine IL-1β successfully reduces the incidence of secondary CV events. This review briefly assesses the role of inflammation in atherosclerosis, providing a picture of the multiple players involved in the process and offering a perspective on targeting inflammation to prevent atherosclerotic CV events, as well as focusing on the results of the latest Phase III clinical trials.

scholarly journals Macrophage Polarization in Chronic Lymphocytic Leukemia: Nurse-Like Cells Are the Caretakers of Leukemic Cells

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 516
Author(s):  
Oana Mesaros ◽  
Laura Jimbu ◽  
Alexandra Neaga ◽  
Cristian Popescu ◽  
Iulia Berceanu ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Current Knowledge ◽  
Macrophage Polarization ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Dominant Phenotype ◽  
Cytokines And Chemokines ◽  
Neoplastic Process ◽  
M1 Type

Macrophages are terminally differentiated innate immune cells. Through their activation, they can be polarized towards the pro-inflammatory M1 type or the wound healing-associated, anti-inflammatory M2 type macrophages. In the tumor microenvironment (TME), M2 is the dominant phenotype and these cells are referred to as tumor-associated macrophages (TAMs). TAMs secrete cytokines and chemokines, exerting an antiapoptotic, proliferative and pro-metastatic effect on the tumor cells. TAMs can be found in many cancers, including chronic lymphocytic leukemia (CLL), where they are called nurse-like cells (NLCs). Despite the generally indolent behavior of CLL, the proportion of treatment-refractory patients is significant. As with the majority of cancers, despite significant recent progress, CLL pathogenesis is poorly understood. The emerging role of the TME in nurturing the neoplastic process warrants the investigation of macrophages as a significant pathogenetic element of tumors. In this paper, we review the current knowledge on the role of stromal macrophages in CLL.

scholarly journals Az idült májbetegségek progressziójához vezető folyamatok

2016 ◽  
Vol 157 (8) ◽  
pp. 290-297 ◽  
Author(s):  
Anna Egresi ◽  
Gabriella Lengyel ◽  
Anikó Somogyi ◽  
Anna Blázovics ◽  
Krisztina Hagymási
Keyword(s):  
Disease Progression ◽  
Metabolic Diseases ◽  
Treatment Options ◽  
Liver Steatosis ◽  
Intestinal Flora ◽  
Underlying Disease ◽  
Number Of Factors ◽  
Toxic Agents ◽  
Autoimmune Processes

As the result of various effects (viruses, metabolic diseases, nutritional factors, toxic agents, autoimmune processes) abnormal liver function, liver steatosis and connective tissue remodeling may develop. Progression of this process is complex including various pathways and a number of factors. The authors summarize the factors involved in the progression of chronic liver disease. They describe the role of cells and the produced inflammatory mediators and cytokines, as well as the relationship between the disease and the intestinal flora. They emphasize the role of oxidative stress, mitochondrial dysfunction and cell death in disease progression. Insulin resistance and micro-elements (iron, copper) in relation to liver damage are also discussed, and genetic and epigenetic aspects underlying disease progression are summarized. Discovery of novel treatment options, assessment of the effectiveness of treatment, as well as the success and proper timing of liver transplantation may depend on a better understanding of the process of disease progression. Orv. Hetil., 2016, 157(8), 290–297.

scholarly journals Treponema denticola dentilisin triggered TLR2/MyD88 activation upregulates a tissue destructive program involving MMPs via Sp1 in human oral cells

2021 ◽  
Author(s):  
Sean Ganther ◽  
Allan Radaic ◽  
Nick Chang ◽  
Christian Tafolla ◽  
Ling Zhan ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Periodontal Disease ◽  
Disease Progression ◽  
Inflammatory Cytokines ◽  
Oral Microbiome ◽  
Treponema Denticola ◽  
Periodontal Tissue ◽  
Cellular Processes ◽  
Pro Inflammatory Cytokines

ABSTRACTPeriodontal disease is driven by dysbiosis of the oral microbiome, resulting in over-representation of species that induce the release of pro-inflammatory cytokines, chemokines, and tissue-remodeling matrix metalloproteinases (MMPs) in the periodontium. These chronic tissue-destructive inflammatory responses result in gradual loss of tooth-supporting alveolar bone. The oral spirochete Treponema denticola, is consistently found at significantly elevated levels in periodontal lesions. Host-expressed Toll-Like Receptor 2 (TLR2) senses a variety of bacterial ligands, including acylated lipopolysaccharides and lipoproteins. T. denticola dentilisin, a surface-expressed protease complex comprised of three lipoproteins has been implicated as a virulence factor in periodontal disease, primarily due to its proteolytic activity. While the role of acylated bacterial components in induction of inflammation is well-studied, little attention has been given to the potential role of the acylated nature of dentilisin. The purpose of this study was to test the hypothesis that T. denticola dentilisin activates a TLR2-dependent mechanism, leading to upregulation of tissue-destructive genes in periodontal tissue. RNA-sequencing of periodontal ligament cells challenged with T. denticola bacteria revealed a significant upregulation of genes associated with extracellular matrix organization and degradation, including tissue-specific inducible MMPs that may play novel roles in modulating host immune responses yet to be characterized within the context of oral disease. The Gram-negative oral commensal, Veillonella parvula, failed to upregulate these same MMPs. Dentilisin-induced upregulation of MMPs was mediated via TLR2 and MyD88 activation, since knockdown of either TLR2 or MyD88 abrogated these effects. Challenge with purified dentilisin upregulated the same MMPs, whereas a dentilisin-deficient T. denticola mutant had no effect. Finally, T. denticola-mediated activation of TLR2/MyD88 led to the nuclear translocation of the transcription factor Sp1, which was shown to be a critical regulator of all T. denticola-dependent MMP expression. Taken together, these data support that T. denticola dentilisin stimulates tissue-destructive cellular processes in a TLR2/MyD88/Sp1-dependent fashion.AUTHOR SUMMARYPeriodontal disease is driven by dysbiosis of the oral microbiome, which interacts with host tissues and thereby induces the release of pro-inflammatory cytokines, chemokines, and tissue-remodeling matrix metalloproteinases (MMPs), leading to destruction of the periodontal tissues. Even after clinical intervention, patients with severe periodontal disease are left with a persistent pro-inflammatory transcriptional profile throughout the periodontium. The oral spirochete, Treponema denticola, is consistently found at elevated levels in periodontal lesions and is associated with several pathophysiological effects driving periodontal disease progression. The T. denticola surface-expressed protease complex (dentilisin) has cytopathic effects consistent with periodontal disease pathogenesis. To date, few direct links have been reported between dentilisin and the cellular and tissue processes that drive periodontal tissue destruction at the transcriptional and/or epigenetic levels. Here, we utilize wild type and dentilisin-deficient T. denticola as well as purified dentilisin to characterize dentilisin-dependent activation of intracellular pathways controlling MMP expression and activity. Our results define a role for dentilisin in initiating this signal cascade. Also, our study identified tissue-specific inducible MMPs that may play novel roles in modulating as-yet uncharacterized host responses in periodontal disease. Lastly, T. denticola dentilisin stimulates tissue-destructive cellular processes in a TLR2/MyD88/Sp1-dependent fashion. Taken together, our study provides new insights into the molecular mechanisms underpinning periodontal disease progression which could lead to the development of more efficacious therapeutic treatments.

scholarly journals Delayed Gut Colonization Shapes Future Allergic Responses in a Murine Model of Atopic Dermatitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Amalie W. Arildsen ◽  
Line F. Zachariassen ◽  
Lukasz Krych ◽  
Axel K. Hansen ◽  
Camilla H. F. Hansen
Keyword(s):  
Atopic Dermatitis ◽  
Immunological Response ◽  
Epidemiological Studies ◽  
Microbial Colonization ◽  
Cytokines And Chemokines ◽  
Gut Colonization ◽  
Histological Score ◽  
The Status ◽  
Pro Inflammatory Cytokines

Epidemiological studies have long reported that perturbations of the childhood microbiome increase the risk of developing allergies, but a causal relationship with atopic dermatitis remains unclear. Here we colonized germ-free mice at birth or at one or eight week-of-age to investigate the role of prenatal and early postnatal microbial exposure on development of oxozolone-induced dermatitis later in life. We demonstrate that only one week delayed microbial colonization increased IgE levels and the total histological score of the inflamed ear compared to mice colonized throughout life. In parallel, several pro-inflammatory cytokines and chemokines were upregulated in the ear tissue demonstrating an enhanced immunological response following delayed postnatal colonization of the gut. In contrast, sensitivity to oxazolone-induced dermatitis was unaffected by the presence of a maternal microbiota during gestation. Mice colonized at eight week-of-age failed to colonize Rikenellaceae, a group of bacteria previously associated with a high-responding phenotype, and did not develop an immunological response to the same extent as the early colonized mice despite pronounced histopathological manifestations. The study provides proof-of-principle that the first intestinal colonizers of mice pups are crucial for the development of oxazolone-induced dermatitis later in life, and that the status of the maternal microbiota during pregnancy has no influence on the offspring’s allergic immune response. This highlights an important window of opportunity following birth for microbiota-mediated interventions to prevent atopic responses later in life. How long such a window is open may vary between mice and humans considering species differences in the ontogeny of the immune system.

scholarly journals The ARTEMIS Center: An Environmental Health Prevention Platform Dedicated to Reproduction

2020 ◽  
Vol 17 (3) ◽  
pp. 694
Author(s):  
Fleur Delva ◽  
Guyguy Manangama ◽  
Patrick Brochard ◽  
Raphaëlle Teysseire ◽  
Loïc Sentilhes
Keyword(s):  
Risk Factor ◽  
Environmental Health ◽  
Pesticide Exposure ◽  
Preventive Action ◽  
New Approach ◽  
Reproductive Risk ◽  
Preventive Actions ◽  
Standardized Interview ◽  
The Individual

In France, a new approach is being developed through the ARTEMIS Center, which is a prevention platform for environmental health dedicated to reproduction. The objective is to describe the clinical management of patients in the ARTEMIS center. Couples with a condition affecting reproduction are referred to the ARTEMIS center. Management includes a medical consultation and a standardized interview. Current exposure is assessed by a questionnaire that includes exposure circumstances to reproductive risk factor and on the basis of which it is possible to implement preventive action in clinical practice without prejudging the role of such exposure in the onset of disease. From 16 February 2016 to 2 May 2019, 779 patients were seen in the ARTEMIS center. On the day of the consultation, 88.3% men and 72.2% women were employed. Among employed men, 61.5% had at least one instance of occupational exposure to a reproductive risk factor, and among employed women, 57.8%. The main nonprofessional circumstances of exposure identified were proximity of the residence to an agricultural area (35.3%) and domestic pesticide exposure (79.7%). The preventive actions implemented by the ARTEMIS center are targeted to the individual practices of patients. However, patient care also allows their physicians to become familiarized with environmental health.

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