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1.
Iron Oxide Particles Alter Bacterial Uptake and the LPS-Induced Inflammatory Response in Macrophages.
Williams, LJ, Tristram, SG, Zosky, GR
International journal of environmental research and public health. 2020;(1)
Abstract
Exposure to geogenic (earth-derived) particulate matter (PM) is linked to severe bacterial infections in Australian Aboriginal communities. Experimental studies have shown that the concentration of iron in geogenic PM is associated with the magnitude of respiratory health effects, however, the mechanism is unclear. We investigated the effect of silica and iron oxide on the inflammatory response and bacterial phagocytosis in macrophages. THP-1 and peripheral blood mononuclear cell-derived macrophages were exposed to iron oxide (haematite or magnetite) or silica PM with or without exposure to lipopolysaccharide. Cytotoxicity and inflammation were assessed by LDH assay and ELISA respectively. The uptake of non-typeable Haemophilus influenzae by macrophages was quantified by flow cytometry. Iron oxide increased IL-8 production while silica also induced significant production of IL-1β. Both iron oxide and silica enhanced LPS-induced production of TNF-α, IL-1β, IL-6 and IL-8 in THP-1 cells with most of these responses replicated in PBMCs. While silica had no effect on NTHi phagocytosis, iron oxide significantly impaired this response. These data suggest that geogenic particles, particularly iron oxide PM, cause inflammatory cytokine production in macrophages and impair bacterial phagocytosis. These responses do not appear to be linked. This provides a possible mechanism for the link between exposure to these particles and severe bacterial infection.
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Neuromuscular electrical stimulation and protein during bed rest increases CD11b+ skeletal muscle macrophages but does not correspond to muscle size or insulin sensitivity.
Reidy, PT, Edvalson, LT, McKenzie, AI, Petrocelli, JJ, Mahmassani, ZS, Drummond, MJ
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2020;(11):1261-1269
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Abstract
With this cohort, we previously demonstrated preservation of thigh lean tissue with neuromuscular electrical stimulation combined with protein supplementation (NMES+PRO) treatment during bed rest in healthy older adults. Because macrophage polarization plays a significant role in the repair and maintenance of muscle size and insulin sensitivity, we hypothesized that muscle macrophages would be induced by NMES+PRO and would correspond to an increase in lean mass and an attenuated insulin resistance response altered by bed rest. Older adults (60-80 years old; body mass index < 30 kg/m2) underwent 5 days of bed rest and were randomized to either thrice daily treatment of NMES+PRO (n = 8) or CON (n = 8). Lean mass, insulin sensitivity, and markers of muscle macrophages, inflammation, and connective tissue were determined before and after bed rest. Glucose intolerance and insulin resistance occurred after bed rest but there was not a treatment effect (p > 0.10). Proinflammatory-like macrophages (CD11b+, CD206-) increased (p < 0.05) with NMES+PRO treatment and was different than CON. Minor changes in noncontractile tissue were observed. However, changes in muscle macrophages or extracellular matrix were not related to the preservation of thigh lean mass or insulin resistance. Daily NMES+PRO treatment during bed rest induced a muscle proinflammatory-like macrophage response and was unrelated to muscle size or metabolic function. This study is listed as clinical trial NCT02566590. Novelty Neuromuscular electrical stimulation combined with protein supplementation (NMES+PRO) increased proinflammatory-like macrophages and extracellular matrix content in older adults after bed rest. NMES+PRO changes in macrophages and noncontractile tissue macrophages were not related to muscle size preservation or insulin sensitivity.
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Alcoholic and Non-Alcoholic Beer Modulate Plasma and Macrophage microRNAs Differently in a Pilot Intervention in Humans with Cardiovascular Risk.
Daimiel, L, Micó, V, Díez-Ricote, L, Ruiz-Valderrey, P, Istas, G, Rodríguez-Mateos, A, Ordovás, JM
Nutrients. 2020;(1)
Abstract
Beer is a popular beverage and some beneficial effects have been attributed to its moderate consumption. We carried out a pilot study to test if beer and non-alcoholic beer consumption modify the levels of a panel of 53 cardiometabolic microRNAs in plasma and macrophages. Seven non-smoker men aged 30-65 with high cardiovascular risk were recruited for a non-randomised cross-over intervention consisting of the ingestion of 500 mL/day of beer or non-alcoholic beer for 14 days with a 7-day washout period between interventions. Plasma and urine isoxanthohumol were measured to assess compliance with interventions. Monocytes were isolated and differentiated into macrophages, and plasma and macrophage microRNAs were analysed by quantitative real-time PCR. Anthropometric, biochemistry and dietary parameters were also measured. We found an increase in plasma miR-155-5p, miR-328-3p, and miR-92a-3p after beer and a decrease after non-alcoholic beer consumption. Plasma miR-320a-3p levels decreased with both beers. Circulating miR-320a-3p levels correlated with LDL-cholesterol. We found that miR-17-5p, miR-20a-5p, miR-145-5p, miR-26b-5p, and miR-223-3p macrophage levels increased after beer and decreased after non-alcoholic beer consumption. Functional analyses suggested that modulated microRNAs were involved in catabolism, nutrient sensing, Toll-like receptors signalling and inflammation. We concluded that beer and non-alcoholic beer intake modulated differentially plasma and macrophage microRNAs. Specifically, microRNAs related to inflammation increased after beer consumption and decreased after non-alcoholic beer consumption.
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Legumain is upregulated in acute cardiovascular events and associated with improved outcome - potentially related to anti-inflammatory effects on macrophages.
Lunde, NN, Gregersen, I, Ueland, T, Shetelig, C, Holm, S, Kong, XY, Michelsen, AE, Otterdal, K, Yndestad, A, Broch, K, et al
Atherosclerosis. 2020;:74-82
Abstract
BACKGROUND AND AIMS We have previously found increased levels of the cysteine protease legumain in plasma and plaques from patients with carotid atherosclerosis. This study further investigated legumain during acute cardiovascular events. METHODS Circulating levels of legumain from patients and legumain released from platelets were assessed by enzyme-linked-immunosorbent assay. Quantitative PCR and immunoblotting were used to study expression, while localization was visualized by immunohistochemistry. RESULTS In the SUMMIT Malmö cohort (n = 339 with or without type 2 diabetes and/or cardiovascular disease [CVD], and 64 healthy controls), the levels of circulating legumain were associated with the presence of CVD in non-diabetics, with no relation to outcome. In symptomatic carotid plaques and in samples from both coronary and intracerebral thrombi obtained during acute cardiovascular events, legumain was co-localized with macrophages in the same regions as platelets. In vitro, legumain was shown to be present in and released from platelets upon activation. In addition, THP-1 macrophages exposed to releasate from activated platelets showed increased legumain expression. Interestingly, primary peripheral blood mononuclear cells stimulated with recombinant legumain promoted anti-inflammatory responses. Finally, in a STEMI population (POSTEMI; n = 272), patients had significantly higher circulating legumain before and immediately after percutaneous coronary intervention compared with healthy controls (n = 67), and high levels were associated with improved outcome. CONCLUSIONS Our data demonstrate for the first time that legumain is upregulated during acute cardiovascular events and is associated with improved outcome.
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Folate and macrophage folate receptor-β in idiopathic pulmonary fibrosis disease: the potential therapeutic target?
Qu, Y, Hao, C, Zhai, R, Yao, W
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2020;:110711
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, fatal disease with high mortality and poor prognosis. It is characterized by a gradual decline in lung function, and there are currently no effective therapeutic methods. Folate is a water-soluble B vitamin that plays an important role in one-carbon transfer reactions, nucleic acid biosynthesis and methylation reactions. Studies have shown that folate may participate in the pathogenesis of IPF through ways of DNA repair, methylation, and reactive oxygen species. Macrophage activation is an important early cellular event in IPF and the inflammatory response that they trigger is a significant feature of IPF. Folate receptor-β (FR-β) is a cell surface glycosylphosphatidylinositol-anchored glycoprotein that can mediate the unidirectional transport of folate into cells. And it has been found in previous studies that FR-β is usually overexpressed on activated macrophages, but the expression on resting macrophages was undetectable. Therefore, targeting FR-β may have potential value for the early diagnosis and therapy of IPF. Our goal is to highlight the biological role of folate and FR-β in IPF, and we hope to provide helpful insight for clinical treatment strategies.
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Macrophage Cholesterol Efflux Downregulation Is Not Associated with Abdominal Aortic Aneurysm (AAA) Progression.
Canyelles, M, Tondo, M, Lindholt, JS, Santos, D, Fernández-Alonso, I, de Gonzalo-Calvo, D, Blanco-Colio, LM, Escolà-Gil, JC, Martín-Ventura, JL, Blanco-Vaca, F
Biomolecules. 2020;(4)
Abstract
Recent studies have raised the possibility of a role for lipoproteins, including high-density lipoprotein cholesterol (HDLc), in abdominal aortic aneurysm (AAA). The study was conducted in plasmas from 39 large size AAA patients (aortic diameter > 50 mm), 81 small/medium size AAA patients (aortic diameter between 30 and 50 mm) and 38 control subjects (aortic diameter < 30 mm). We evaluated the potential of HDL-mediated macrophage cholesterol efflux (MCE) to predict AAA growth and/or the need for surgery. MCE was impaired in the large aortic diameter AAA group as compared with that in the small/medium size AAA group and the control group. However, no significant difference in HDL-mediated MCE capacity was observed in 3 different progression subgroups (classified according to growth rate < 1 mm per year, between 1 and 5 mm per year or >5 mm per year) in patients with small/medium size AAA. Moreover, no correlation was found between MCE capacity and the aneurysm growth rate. A multivariate Cox regression analysis revealed a significant association between lower MCE capacity with the need for surgery in all AAA patients. Nevertheless, the significance was lost when only small/medium size AAA patients were included. Our results suggest that MCE, a major HDL functional activity, is not involved in AAA progression.
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Impaired Cholesterol-Uptake Capacity of HDL Might Promote Target-Lesion Revascularization by Inducing Neoatherosclerosis After Stent Implantation.
Nagano, Y, Otake, H, Toba, T, Kuroda, K, Shinkura, Y, Tahara, N, Tsukiyama, Y, Yanaka, K, Yamamoto, H, Nagasawa, A, et al
Journal of the American Heart Association. 2019;(9):e011975
Abstract
Background We evaluated the importance of high-density lipoprotein (HDL) functionality for target-lesion revascularization in patients treated with coronary stents using a rapid cell-free assay system to evaluate the functional capacity of HDL to accept additional cholesterol (cholesterol-uptake capacity; CUC). Methods and Results From an optical coherence tomography (OCT) registry of patients treated with coronary stents, 207 patients were enrolled and their HDL was functionally evaluated by measuring the CUC. Follow-up OCT was performed (median duration, 24.5 months after stenting) to evaluate the presence of neoatherosclerosis. Clinical follow-up was performed to assess target-lesion revascularization for a median duration of 42.3 months after stent implantation. Neoatherosclerosis was identified in 37 patients (17.9%). Multivariate logistic regression analysis revealed that a decreased CUC was independently associated with neoatherosclerosis (odds ratio, 0.799; P<0.001). The CUC showed a significant inverse correlation with incidence of target-lesion revascularization (odds ratio, 0.887; P=0.003) and with lipid accumulation inside stents, suggesting that neoatherosclerosis contributes to the association between CUC and target-lesion revascularization. Conclusions Impaired HDL functionality, detected as decreased CUC, might lead to future stent failure by provoking atherogenic changes of the neointima within stents. Both quantitative and qualitative assessments of HDL might enable the improved prediction of clinical outcomes after stent implantation.
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Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage.
Borrajo, A, Ranazzi, A, Pollicita, M, Bellocchi, MC, Salpini, R, Mauro, MV, Ceccherini-Silberstein, F, Perno, CF, Svicher, V, Aquaro, S
Medicina (Kaunas, Lithuania). 2019;(6)
Abstract
Background and objectives: To enter the target cell, HIV-1 binds not only CD4 but also a co-receptor β-chemokine receptor 5 (CCR5) or α chemokine receptor 4 (CXCR4). Limited information is available on the impact of co-receptor usage on HIV-1 replication in monocyte-derived macrophages (MDM) and on the homeostasis of this important cellular reservoir. Materials and Methods: Replication (measured by p24 production) of the CCR5-tropic 81A strain increased up to 10 days post-infection and then reached a plateau. Conversely, the replication of the CXCR4-tropic NL4.3 strain (after an initial increase up to day 7) underwent a drastic decrease becoming almost undetectable after 10 days post-infection. The ability of CCR5-tropic and CXCR4-tropic strains to induce cell death in MDM was then evaluated. While for CCR5-tropic 81A the rate of apoptosis in MDM was comparable to uninfected MDM, the infection of CXCR4-tropic NL4.3 in MDM was associated with a rate of 14.3% of apoptotic cells at day 6 reaching a peak of 43.5% at day 10 post-infection. Results: This suggests that the decrease in CXCR4-tropic strain replication in MDM can be due to their ability to induce cell death in MDM. The increase in apoptosis was paralleled with a 2-fold increase in the phosphorylated form of p38 compared to WT. Furthermore, microarray analysis showed modulation of proapoptotic and cancer-related genes induced by CXCR4-tropic strains starting from 24 h after infection, whereas CCR5 viruses modulated the expression of genes not correlated with apoptotic-pathways. Conclusions: In conclusion, CXCR4-tropic strains can induce a remarkable depletion of MDM. Conversely, MDM can represent an important cellular reservoir for CCR5-tropic strains supporting the role of CCR5-usage in HIV-1 pathogenesis and as a pharmacological target to contribute to an HIV-1 cure.
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Survival of an epidemic MDR strain of Mycobacterium tuberculosis and its non-prosperous variant within activated macrophages.
Yokobori, N, Monteserin, J, Rearte, B, Paul, R, Símboli, N, López, B, Ritacco, V, Sasiain, MDC
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2019;:248-254
Abstract
The fitness of a pathogen results from the interaction of multiple factors favoring either epidemiological success or failure. Herein, we studied the performance of the M strain, a highly successful multidrug resistant Mycobacterium tuberculosis genotype, and its non-prosperous variant, the 410 strain, in activated human monocyte-derived macrophages. Both strains showed comparable ability to induce necrotic cell death and to survive in apoptotic macrophages. Of the various macrophage activation conditions tested, none led to an enhanced control of the outbreak strain. The combination of 1,25(OH)2 vitaminD3 and IFN-γ favored significantly the control of the non-prosperous 410 strain. These observations indicate that the ability of the M strain to survive within the hostile intracellular milieu is conserved, and the overall fitness cost paid by this genotype would be low. Our results provide additional evidence on bacterial traits that may have contributed to the epidemiological success of the M strain.
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10.
[The immunomodulatory role of sodium].
Agócs, RI, Sugár, D, Pap, D, Szabó, AJ
Orvosi hetilap. 2019;(17):646-653
Abstract
High salt intake, which is common in the Western world, is the cause of several lifestyle diseases. Recent investigations shed light on novel extrarenal processes, which play role in the maintenance of sodium balance. In the short term, sodium storage of the skin may serve as a buffer against volume overload arising from the osmotic properties of sodium. Increased tissue sodium concentration may also potentiate immune response against infections. In the long run, however, tissue sodium concentration over a certain limit may initiate pathophysiological processes by provoking inflammatory response. Due to the immune modulating role of sodium, the effector cells of the innate as well as the adaptive immune system are activated, while certain regulator cells of the same systems are repressed, ultimately resulting in a proinflammatory state characterized by the imbalance of the immune system. Experiments applying dietary salt overload/salt depletion imply the role of sodium in the initiation/exacerbation of several diseases. Thus the relationship between sodium and the immune system may give an explanation to the pathomechanism of diseases with so far unknown origin such as hypertonia (primary, salt sensitive) or autoimmune diseases - all these putting tremendous pressure on the healthcare system due to their increasing incidence. Orv Hetil. 2019; 160(17): 646-653.