scholarly journals Evaluation of the immunomodulatory effects of cobalt, copper and magnesium ions in a pro inflammatory environment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Leire Díez-Tercero ◽  
Luis M. Delgado ◽  
Elia Bosch-Rué ◽  
Roman A. Perez
Keyword(s):  
Inflammatory Marker ◽  
Macrophage Polarization ◽  
Innate Immune ◽  
Magnesium Ions ◽  
Immunomodulatory Effects ◽  
Limited Evidence ◽  
Macrophage Response ◽  
Inflammatory Phenotype ◽  
Marker Expression ◽  
Immunomodulatory Potential

AbstractBiomaterials and scaffolds for Tissue Engineering are widely used for an effective healing and regeneration. However, the implantation of these scaffolds causes an innate immune response in which the macrophage polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype is crucial to avoid chronic inflammation. Recent studies have showed that the use of bioactive ions such as cobalt (Co2+), copper (Cu2+) and magnesium (Mg2+) could improve tissue regeneration, although there is limited evidence on their effect on the macrophage response. Therefore, we investigated the immunomodulatory potential of Co2+, Cu2+ and Mg2+ in macrophage polarization. Our results indicate that Mg2+ and concentrations of Cu2+ lower than 10 μM promoted the expression of M2 related genes. However, higher concentrations of Cu2+ and Co2+ (100 μM) stimulated pro-inflammatory marker expression, indicating a concentration dependent effect of these ions. Furthermore, Mg2+ were able to decrease M1 marker expression in presence of a mild pro-inflammatory stimulus, showing that Mg2+ can be used to modulate the inflammatory response, even though their application can be limited in a strong pro-inflammatory environment.

scholarly journals Microbial co-infection alters macrophage polarization, phagosomal escape, and microbial killing

2018 ◽  
Vol 24 (3) ◽  
pp. 152-162 ◽  
Author(s):  
Nikita H Trivedi ◽  
Jieh-Juen Yu ◽  
Chiung-Yu Hung ◽  
Richard P Doelger ◽  
Christopher S Navara ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Macrophage Activation ◽  
Secondary Infection ◽  
Macrophage Polarization ◽  
Innate Immune ◽  
No Production ◽  
Bacterial Killing ◽  
Macrophage Response ◽  
Endosomal Acidification ◽  
J774 Cells

Macrophages are important innate immune cells that respond to microbial insults. In response to multi-bacterial infection, the macrophage activation state may change upon exposure to nascent mediators, which results in different bacterial killing mechanism(s). In this study, we utilized two respiratory bacterial pathogens, Mycobacterium bovis (Bacillus Calmette Guẻrin, BCG) and Francisella tularensis live vaccine strain (LVS) with different phagocyte evasion mechanisms, as model microbes to assess the influence of initial bacterial infection on the macrophage response to secondary infection. Non-activated (M0) macrophages or activated M2-polarized cells (J774 cells transfected with the mouse IL-4 gene) were first infected with BCG for 24–48 h, subsequently challenged with LVS, and the results of inhibition of LVS replication in the macrophages was assessed. BCG infection in M0 macrophages activated TLR2-MyD88 and Mincle-CARD9 signaling pathways, stimulating nitric oxide (NO) production and enhanced killing of LVS. BCG infection had little effect on LVS escape from phagosomes into the cytosol in M0 macrophages. In contrast, M2-polarized macrophages exhibited enhanced endosomal acidification, as well as inhibiting LVS replication. Pre-infection with BCG did not induce NO production and thus did not further reduce LVS replication. This study provides a model for studies of the complexity of macrophage activation in response to multi-bacterial infection.

scholarly journals phage surface induced modulation of inflammatory responses

2021 ◽  
Author(s):  
Zohreh Safari ◽  
Majid Sadeghizadeh ◽  
Ahmad Zavaran Hosseini ◽  
Hassan Bardaania ◽  
Sara Soudi
Keyword(s):  
Tissue Engineering ◽  
Immune Reaction ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Morphological Characteristics ◽  
Innate Immune ◽  
Main Function ◽  
Nano Structure ◽  
Inflammatory Phenotype ◽  
And Function

Chronic inflammation responses hamper the tissue engineering. immune system has main function in the regeneration and maintenance of all tissue, the immune reaction to an implant begins by the innate immune cells including macrophages which can eventually lead to accept or reject of the implant. to avoid adverse immune reactions, current strategies use of immunomodulatory biomaterials rather than inert materials. The present study aimed to introduce as biomaterial is capable of modulating macrophage responses. Macrophages cultured on top of four surfaces then analysis morphological characteristics, cellular outgrowth and function. In addition, measured the key cytokine/chemokine markers of macrophage polarization in each sample. The results of our study pointed out that phage nano-structure can modulate polarization of macrophages toward anti-inflammatory phenotype over time. In addition, the combination of well-characterized RGD peptide motif embedded in bacteriophages can stimulate macrophages to gain regenerative M2-like phenotype more effectively and it may introduce an Immuno-modulating biomaterial for tissue engineering applications.

scholarly journals Microvesicles carrying LRP5 induce macrophage polarization to an anti‐inflammatory phenotype

2021 ◽  
Author(s):  
Aureli Luquero ◽  
Gemma Vilahur ◽  
Javier Crespo ◽  
Lina Badimon ◽  
Maria Borrell‐Pages
Keyword(s):  
Macrophage Polarization ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

scholarly journals Comparative Phenotypic and Functional Analyses of the Effects of IL-10 or TGF-β on Porcine Macrophages

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1098
Author(s):  
Tania Carta ◽  
Elisabetta Razzuoli ◽  
Floriana Fruscione ◽  
Susanna Zinellu ◽  
Dionigia Meloni ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Phagocytic Cells ◽  
Mhc Ii ◽  
Tnf Α ◽  
Regulated Expression ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory ◽  
Functional Analyses ◽  
The Impact ◽  
Immunosuppressive Cytokines

Macrophages are phagocytic cells involved in maintaining tissue homeostasis and defense against pathogens. Macrophages may be polarized into different functionally specialized subsets. M2c macrophages arise following stimulation with IL-10 or TGF-β and mediate anti-inflammatory and tissue repair functions. M2c macrophages remain poorly characterized in the pig, thus we investigated the impact of these regulatory cytokines on porcine monocyte-derived macrophages (moMΦ). The phenotype and functionality of these cells was characterized though confocal microscopy, flow cytometry, ELISA, and RT-qPCR. Both cytokines induced CD14 and MHC II DR down-regulation and reduced IL-6, TNF-α, and CD14 expression, suggestive of an anti-inflammatory phenotype. Interestingly, neither IL-10 or TGF-β were able to trigger IL-10 induction or release by moMΦ. Differences between these cytokines were observed: stimulation with IL-10, but not TGF-β, induced up-regulation of both CD16 and CD163 on moMΦ. In addition, IL-10 down-regulated expression of IL-1β and IL-12p40 4h post-stimulation and induced a stronger impairment of moMΦ ability to respond to either TLR2 or TLR4 agonists. Overall, our results provide an overview of porcine macrophage polarization by two immunosuppressive cytokines, revealing differences between IL-10 and TGF-β, and reporting some peculiarity of swine, which should be considered in translational studies.

Abstract 74: The Nox4 Inhibitor GKT137831, Prevents Aldosterone Production by Adipocytes and Protects Against Adipose Tissue Inflammation and Fibrosis in Obese Mice

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Sarah Even ◽  
Aurelie Nguyen Dinh Cat ◽  
Francisco J Rios ◽  
Antunes T Tayze ◽  
Ying He ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Culture Media ◽  
Inflammatory Marker ◽  
High Dose ◽  
Obese Mice ◽  
Cardiovascular Damage ◽  
Aldosterone Production ◽  
Inflammatory Phenotype ◽  
Sirius Red

Aldosterone (aldo) plays an important role in obesity-associated cardiovascular risk. We demonstrated that aldo is produced by adipocytes, an effect associated with increased generation of reactive oxygen species (ROS). These processes are exaggerated in obesity. The relationship between adipocyte aldosterone and ROS is unclear. We postulated that Nox4-derived ROS is important for aldo production in adipocytes and leads to a pro-inflammatory phenotype in obesity. Studies were performed in db/m (lean) and db/db (obese) mice, treated with low (20mg/kg/day) or high dose (60mg/kg/day) GKT137831 (GKT, Nox4 inhibitor, 16 weeks). Epididymal (EVAT) and perivascular (PVAT) fat were collected. Plasma and adipocyte aldo were measured by ELISA. Adipose tissue fibrosis was evaluated by picro Sirius red staining and inflammatory mediators by immunostudies. Body weight was increased in db/db mice (61.8g vs control 33.5g), with no effect of GKT. Epididymal adiposity was increased in db/db mice (0.098g vs. 0.067g, p<0.05). Plasma aldo levels in db/db (pg/mL: 518 vs. 272g) and aldo levels in culture media from db/db adipocytes were increased (pg/mL/μg RNA: 1964 vs. 388), p<0.05. All effects decreased by high dose GKT. In PVAT, CYP11B2 gene expression was increased in db/db (2.6±0.8 vs control 1.1±0.1, p<0.05), an effect blocked by Nox4 inhibition. Gene expression of adipocyte differentiation marker, AP2, was increased (3.5±1.1 vs control 1.4±0.4) while anti-inflammatory marker adiponectin was decreased (0.7±0.1 vs control 1.3±0.2, p<0.05)) in obese mice. GKT decreased AP2 levels. Adipocyte-derived TNFα was increased in db/db (4.9±1.8 vs control 1.6±0.6, p<0.05), an effect blocked by GKT. Pro-collagen I, marker of fibrosis, was increased in db/db mice (132±11 vs control 87±4, p<0.05). Sirius red staining was exaggerated in EVAT from db/db mice, and decreased by Nox4 inhibition. In conclusion, Nox4 plays a role in regulating adipocyte-derived aldosterone and promotes a pro-inflammatory and profibrotic adipose phenotype in obese db/db mice. These findings suggest that adipocyte Nox4 links hyperaldosteronism and inflammation/fibrosis in adiposity and as such may be a putative therapeutic target for obesity-associated cardiovascular damage.

scholarly journals Ironing Out the Details: How Iron Orchestrates Macrophage Polarization

2021 ◽  
Vol 12 ◽  
Author(s):  
Yaoyao Xia ◽  
Yikun Li ◽  
Xiaoyan Wu ◽  
Qingzhuo Zhang ◽  
Siyuan Chen ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Immune Responses ◽  
Epigenetic Regulation ◽  
Crucial Role ◽  
Liver Diseases ◽  
Iron Supplementation ◽  
Macrophage Polarization ◽  
Innate Immune ◽  
Innate Immune Responses

Iron fine-tunes innate immune responses, including macrophage inflammation. In this review, we summarize the current understanding about the iron in dictating macrophage polarization. Mechanistically, iron orchestrates macrophage polarization through several aspects, including cellular signaling, cellular metabolism, and epigenetic regulation. Therefore, iron modulates the development and progression of multiple macrophage-associated diseases, such as cancer, atherosclerosis, and liver diseases. Collectively, this review highlights the crucial role of iron for macrophage polarization, and indicates the potential application of iron supplementation as an adjuvant therapy in different inflammatory disorders relative to the balance of macrophage polarization.

scholarly journals Impaired lymphoid extracellular matrix impedes antibacterial immunity in epidermolysis bullosa

2018 ◽  
Vol 115 (4) ◽  
pp. E705-E714 ◽  
Author(s):  
Alexander Nyström ◽  
Olivier Bornert ◽  
Tobias Kühl ◽  
Christine Gretzmeier ◽  
Kerstin Thriene ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Epidermolysis Bullosa ◽  
Bacterial Colonization ◽  
Mouse Skin ◽  
Innate Immune ◽  
Macrophage Response ◽  
Skin Fragility ◽  
Human Validation ◽  
Spleen And Lymph Nodes ◽  
Collagen Vii

Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB), a skin fragility disorder that, unexpectedly, manifests also with elevated colonization of commensal bacteria and frequent wound infections. Here, we describe an unprecedented systemic function of collagen VII as a member of a unique innate immune-supporting multiprotein complex in spleen and lymph nodes. In this complex, collagen VII specifically binds and sequesters the innate immune activator cochlin in the lumen of lymphoid conduits. In genetic mouse models, loss of collagen VII increased bacterial colonization by diminishing levels of circulating cochlin LCCL domain. Intraperitoneal injection of collagen VII, which restored cochlin in the spleen, but not in the skin, reactivated peripheral innate immune cells via cochlin and reduced bacterial skin colonization. Systemic administration of the cochlin LCCL domain was alone sufficient to diminish bacterial supercolonization of RDEB mouse skin. Human validation demonstrated that RDEB patients displayed lower levels of systemic cochlin LCCL domain with subsequently impaired macrophage response in infected wounds. This study identifies an intrinsic innate immune dysfunction in RDEB and uncovers a unique role of the lymphoid extracellular matrix in systemic defense against bacteria.

scholarly journals The Translocator Protein (TSPO) in Mitochondrial Bioenergetics and Immune Processes

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 512 ◽  
Author(s):  
Calina Betlazar ◽  
Ryan J. Middleton ◽  
Richard Banati ◽  
Guo-Jun Liu
Keyword(s):  
Paradigm Shift ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Translocator Protein ◽  
Imaging Studies ◽  
Immunomodulatory Effects ◽  
Cellular Functions ◽  
Mitochondrial Functions ◽  
Cellular Bioenergetics ◽  
Mitochondrial Membrane Protein

The translocator protein (TSPO) is an outer mitochondrial membrane protein that is widely used as a biomarker of neuroinflammation, being markedly upregulated in activated microglia in a range of brain pathologies. Despite its extensive use as a target in molecular imaging studies, the exact cellular functions of this protein remain in question. The long-held view that TSPO plays a fundamental role in the translocation of cholesterol through the mitochondrial membranes, and thus, steroidogenesis, has been disputed by several groups with the advent of TSPO knockout mouse models. Instead, much evidence is emerging that TSPO plays a fundamental role in cellular bioenergetics and associated mitochondrial functions, also part of a greater role in the innate immune processes of microglia. In this review, we examine the more direct experimental literature surrounding the immunomodulatory effects of TSPO. We also review studies which highlight a more central role for TSPO in mitochondrial processes, from energy metabolism, to the propagation of inflammatory responses through reactive oxygen species (ROS) modulation. In this way, we highlight a paradigm shift in approaches to TSPO functioning.

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