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15 pages, 2642 KiB

Open AccessArticle

Re-Analysis of Single-Nucleus Transcriptomics Reveals Diverse Dorsal Root Ganglia Macrophage Responses Following Peripheral Nerve Injury

by Nea Korvenlaita and Lauri Louhivuori

Biomedicines 2022, 10(12), 3295; https://doi.org/10.3390/biomedicines10123295 - 19 Dec 2022

Cited by 2 | Viewed by 1332

Abstract

An increasing amount of evidence points to an important role of macrophages in peripheral nerve injury (PNI) and associated pain. Peripheral nerve macrophages facilitate the regeneration, while dorsal root ganglia (DRG) macrophages might propagate the injury after a PNI. These differences might be [...] Read more.

An increasing amount of evidence points to an important role of macrophages in peripheral nerve injury (PNI) and associated pain. Peripheral nerve macrophages facilitate the regeneration, while dorsal root ganglia (DRG) macrophages might propagate the injury after a PNI. These differences might be explained by various in vivo models of PNIs or non-uniform methodologies to phenotype the macrophages. Unbiased methods to phenotype macrophages using single whole cell or nucleus transcriptomics have been rarely applied on PNIs outside the nerves themselves. Here, we compare the effects of the transection or crush of the sciatic nerve and spinal nerve transection on the DRG macrophage phenotypes utilizing a publicly available single-nucleus transcriptomic DRG dataset. Our results demonstrate that unique and time-dependent DRG macrophage gene expression profiles were produced by the three PNI models with particular macrophage clusters being enriched that were dependent on the severity of the neuronal injury score. PNI associated DRG macrophages were not purely anti- or pro-inflammatory. These results suggest that various functions of DRG macrophage subtypes are carefully orchestrated upon a PNI. These findings open a new avenue for studying the DRG macrophage subtypes in PNIs and encourage further unbiased phenotyping efforts to better understand their relevance in neuropathic pain. Full article

(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 3.0)

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16 pages, 3572 KiB

Open AccessArticle

Phenolic Compounds Known to Be Present in Lingonberry (Vaccinium vitis-idaea L.) Enhance Macrophage Polarization towards the Anti-Inflammatory M2 Phenotype

by Riitta Ryyti, Mari Hämäläinen, Tiina Leppänen, Rainer Peltola and Eeva Moilanen

Biomedicines 2022, 10(12), 3045; https://doi.org/10.3390/biomedicines10123045 - 25 Nov 2022

Cited by 2 | Viewed by 1564

Abstract

Macrophages are pleiotropic immune cells whose phenotype can polarize towards the pro-inflammatory M1 or anti-inflammatory M2 direction as a response to environmental changes. In obesity, the number of macrophages in adipose tissue is enhanced, and they shift towards the M1 phenotype. Activated M1 [...] Read more.

Macrophages are pleiotropic immune cells whose phenotype can polarize towards the pro-inflammatory M1 or anti-inflammatory M2 direction as a response to environmental changes. In obesity, the number of macrophages in adipose tissue is enhanced, and they shift towards the M1 phenotype. Activated M1 macrophages secrete pro-inflammatory cytokines and adipokines involved in the development of systemic low-grade inflammation, complicating obesity. Polyphenols are widely found in the vegetable kingdom and have anti-inflammatory properties. We and others have recently found that lingonberry (Vaccinium vitis-idaea L.) supplementation is able to prevent the development of low-grade inflammation and its metabolic consequences in experimentally induced obesity. In the present study, we investigated the effects of twelve phenolic compounds known to be present in lingonberry (resveratrol, piceid, quercetin, kaempferol, proanthocyanidins, delphinidin, cyanidin, benzoic acid, cinnamic acid, coumaric acid, caffeic acid, and ferulic acid) on macrophage polarization, which is a meaningful mechanism determining the low-grade inflammation in obesity. Mouse J774 and human U937 macrophages and commercially available phenolic compounds were used in the studies. Three of the twelve compounds investigated showed an effect on macrophage polarization. Resveratrol, kaempferol, and proanthocyanidins enhanced anti-inflammatory M2-type activation, evidenced as increased expression of Arg-1 and MRC-1 in murine macrophages and CCL-17 and MRC-1 in human macrophages. Resveratrol and kaempferol also inhibited pro-inflammatory M1-type activation, shown as decreased expression of IL-6, NO, and MCP-1 in murine macrophages and TNF-α and IL-6 in human macrophages. In the further mechanistic studies, the effects of the three active compounds were investigated on two transcription factors important in M2 activation, namely on PPARγ and STAT6. Resveratrol and kaempferol were found to enhance PPARγ expression, while proanthocyanidins increased the phosphorylation of STAT6. The results suggest proanthocyanidins, resveratrol, and kaempferol as active constituents that may be responsible for the positive anti-inflammatory effects of lingonberry supplementation in obesity models. These data also extend the previous knowledge on the anti-inflammatory effects of lingonberry and encourage further studies to support the use of lingonberry and lingonberry-based products as a part of a healthy diet. Full article

(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 3.0)

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14 pages, 1593 KiB

Open AccessArticle

Macrophage-Targeted Sodium Chlorite (NP001) Slows Progression of Amyotrophic Lateral Sclerosis (ALS) through Regulation of Microbial Translocation

by Rongzhen Zhang, Paige M. Bracci, Ari Azhir, Bruce D. Forrest and Michael S. McGrath

Biomedicines 2022, 10(11), 2907; https://doi.org/10.3390/biomedicines10112907 - 12 Nov 2022

Cited by 4 | Viewed by 3847

Abstract

Amyotrophic lateral sclerosis (ALS) is a heterogeneous, progressive, and universally fatal neurodegenerative disease. A subset of ALS patients has measurable plasma levels of lipopolysaccharide (LPS) and C-reactive protein (CRP) consistent with low-grade microbial translocation (MT). Unless interrupted, MT sets up a self-perpetuating loop [...] Read more.

Amyotrophic lateral sclerosis (ALS) is a heterogeneous, progressive, and universally fatal neurodegenerative disease. A subset of ALS patients has measurable plasma levels of lipopolysaccharide (LPS) and C-reactive protein (CRP) consistent with low-grade microbial translocation (MT). Unless interrupted, MT sets up a self-perpetuating loop of inflammation associated with systemic macrophage activation. To test whether MT contributed to ALS progression, blood specimens from a phase 2 study of NP001 in ALS patients were evaluated for changes in activity in treated patients as compared to controls over the 6-month study. In this post hoc analysis, plasma specimens from baseline and six-month timepoints were analyzed. Compared with baseline values, biomarkers related to MT were significantly decreased (LPS, LPS binding protein (LBP), IL-18, Hepatocyte growth factor (HGF), soluble CD163 (sCD163)) in NP001-treated patients as compared to controls, whereas wound healing and immunoregulatory factors were increased (IL-10, Epidermal growth factor (EGF), neopterin) by the end of study. These biomarker results linked to the positive clinical trial outcome confirm that regulation of macrophage activation may be an effective approach for the treatment of ALS and, potentially, other neuroinflammatory diseases related to MT. Full article

(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 3.0)

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15 pages, 1218 KiB

Open AccessArticle

Effects of Cancer Cell-Derived Nanovesicle Vaccines Produced by the Oxidative Stress-Induced Expression of DAMP and Spontaneous Release/Filter Extrusion in the Interplay of Cancer Cells and Macrophages

by Song-Hsien Lin, Guan-Ying Tsai, Meng-Jiy Wang and Szu-Yuan Chen

Biomedicines 2022, 10(8), 1977; https://doi.org/10.3390/biomedicines10081977 - 15 Aug 2022

Cited by 3 | Viewed by 1467

Abstract

Photodynamic therapy (PDT)-based cancer vaccines are shown to be more effective modalities for treating cancer in animal models compared to other methods used to generate cancer cell-derived vaccines. The higher efficacy seems to stem from the generation of cell membrane nanovesicles or fragments [...] Read more.

Photodynamic therapy (PDT)-based cancer vaccines are shown to be more effective modalities for treating cancer in animal models compared to other methods used to generate cancer cell-derived vaccines. The higher efficacy seems to stem from the generation of cell membrane nanovesicles or fragments that carry both cancer cell-specific antigens and high surface content of damage-associated molecular pattern (DAMP) molecules induced by oxidative stress. To develop more effective cancer vaccines in this direction, we explored the generation of cancer vaccines by applying different sources of oxidative stress on cancer cell cultures followed by spontaneous release or filter extrusions to produce cancer cell-derived DAMP-expressing nanovesicles. Through an in-vitro test based on the co-culture of cancer cells and macrophages, it was found that the nanovesicle vaccines generated by H

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are as effective as those generated by PDT in diminishing cancer cell culture masses, providing a simpler way to manufacture vaccines. In addition, the nanovesicle vaccines produced by filter extrusion are as potent as those produced by spontaneous release, rendering a more stable way for vaccine production. Full article

(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 3.0)

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16 pages, 2514 KiB

Open AccessArticle

Resveratrol and ω-3 PUFAs Promote Human Macrophage Differentiation and Function

by Joseph Schwager, Albine Bompard, Daniel Raederstorff, Hubert Hug and Igor Bendik

Biomedicines 2022, 10(7), 1524; https://doi.org/10.3390/biomedicines10071524 - 28 Jun 2022

Cited by 6 | Viewed by 1983

Abstract

Monocytes differentiate into M1 and M2 macrophages, which are classically activated by microbial products such as LPS or IFN-γ and interleukins (e.g., the anti-inflammatory and T_h2 promoting IL-4), respectively. The contribution of nutrients or nutrient-based substances such as ω-3 polyunsaturated fatty [...] Read more.

Monocytes differentiate into M1 and M2 macrophages, which are classically activated by microbial products such as LPS or IFN-γ and interleukins (e.g., the anti-inflammatory and T_h2 promoting IL-4), respectively. The contribution of nutrients or nutrient-based substances such as ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and resveratrol (Res) on the differentiation and function of M1 and M2 macrophages was evaluated. THP-1 cells and peripheral blood mononuclear cells (PBMCs) were differentiated into M1 and M2 cells and activated with LPS/IFN-γ or IL-4/IL-13. Macrophage lineage specific surface determinants (e.g., CD11b, CD11c, CD14, CD206, CD209, CD274, HLA-DR, CCR7, CCR2) were analysed by cytofluorometry. Res and ω-3 PUFAs altered CD14, CD206, CD274 and HL-DR surface expression patterns in M1 and M2 macrophages differentiated from PBMC. LPS/IFN-γ or IL-14/IL-13 activated macrophages subpopulations, which secreted cytokines and chemokines as measured by multiplex ELISA. Res and ω-3 PUFA reduced IL-1β, IL-6, TNF-α, CXCL10/IP-10, CCL13/MCP-4 and CCL20/MIP-3α in LPS/IFN-γ activated human leukaemia THP-1 cells, which is indicative of a dampening effect on M1 macrophages. However, Res increased M1 prototypic cytokines such as IL-1β or IL-6 in macrophages derived from PBMCs and also modified the expression of IL-12p70. Collectively, Res and ω-3 PUFAs distinctly promoted the differentiation and function of M1 and M2 macrophages. We conclude that these substances strengthen the macrophage-mediated effects on the innate and adaptive immune response. Full article

(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 3.0)

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19 pages, 3655 KiB

Open AccessArticle

Macrophage Phenotype in Combination with Tumor Microbiome Composition Predicts RCC Patients’ Survival: A Pilot Study

by Olga V. Kovaleva, Polina Podlesnaya, Maxim Sorokin, Valeria Mochalnikova, Vladimir Kataev, Yuriy A. Khlopko, Andrey O. Plotnikov, Ivan S. Stilidi, Nikolay E. Kushlinskii and Alexei Gratchev

Biomedicines 2022, 10(7), 1516; https://doi.org/10.3390/biomedicines10071516 - 27 Jun 2022

Cited by 4 | Viewed by 1752

Abstract

The identification of new prognostic markers of renal cell carcinoma (RCC) is an urgent problem in oncourology. To investigate the potential prognostic significance of tumor microbiome and stromal inflammatory markers, we studied a cohort of 66 patients with RCC (23 clear cell RCC, [...] Read more.

The identification of new prognostic markers of renal cell carcinoma (RCC) is an urgent problem in oncourology. To investigate the potential prognostic significance of tumor microbiome and stromal inflammatory markers, we studied a cohort of 66 patients with RCC (23 clear cell RCC, 19 papillary RCC and 24 chromophobe RCC). The microbiome was analyzed in tumor and normal tissue by 16S rRNA amplicon sequencing. Characterization of the tumor stroma was performed using immunohistochemistry. A significant difference in alpha diversity was demonstrated between normal kidney tissue and all types of RCC. Further, we demonstrated that the bacterial burden was higher in adjacent normal tissue than in a tumor. For the first time, we demonstrated a significant correlation between bacterial burden and the content of PU.1+ macrophages and CD66b+ neutrophils in kidney tumors. Tumors with high content of PU.1+ cells and CD66b+ cells in the stroma were characterized by a lower bacterial burden. In the tumors with high bacterial burden, the number of PU.1+ cells and CD66b+ was associated with a poor prognosis. The identified associations indicate the great prognostic potential of a combined tumor microbiome and stromal cell analysis. Full article

(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 3.0)

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17 pages, 4248 KiB

Open AccessArticle

Modulation of Rxrα Expression in Mononuclear Phagocytes Impacts on Cardiac Remodeling after Ischemia-Reperfusion Injury

by Saskia Räuber, Maximilian Fischer, Denise Messerer, Vanessa Wimmler, Kumaraswami Konda, Andrei Todica, Michael Lorenz, Anna Titova, Christian Schulz and Tobias Weinberger

Biomedicines 2022, 10(6), 1274; https://doi.org/10.3390/biomedicines10061274 - 30 May 2022

Viewed by 2076

Abstract

Retinoid X receptors (RXRs), as members of the steroid/thyroid hormone superfamily of nuclear receptors, are crucial regulators of immune response during health and disease. RXR subtype expression is dependent on tissue and cell type, RXRα being the relevant isoform in monocytes and macrophages. [...] Read more.

Retinoid X receptors (RXRs), as members of the steroid/thyroid hormone superfamily of nuclear receptors, are crucial regulators of immune response during health and disease. RXR subtype expression is dependent on tissue and cell type, RXRα being the relevant isoform in monocytes and macrophages. Previous studies have assessed different functions of RXRs and positive implications of RXR agonists on outcomes after ischemic injuries have been described. However, the impact of a reduced Rxrα expression in mononuclear phagocytes on cardiac remodeling after myocardial infarction (MI) has not been investigated to date. Here, we use a temporally controlled deletion of Rxrα in monocytes and macrophages to determine its role in ischemia-reperfusion injury. We show that reduced expression of Rxrα in mononuclear phagocytes leads to a decreased phagocytic activity and an accumulation of apoptotic cells in the myocardium, reduces angiogenesis and cardiac macrophage proliferation in the infarct border zone/infarct area, and has an impact on monocyte/macrophage subset composition. These changes are associated with a greater myocardial defect 30 days after ischemia/reperfusion injury. Overall, the reduction of Rxrα levels in monocytes and macrophages negatively impacts cardiac remodeling after myocardial infarction. Thus, RXRα might represent a therapeutic target to regulate the immune response after MI in order to improve cardiac remodeling. Full article

(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 3.0)

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18 pages, 2955 KiB

Open AccessArticle

Osteocalcin Alleviates Lipopolysaccharide-Induced Acute Inflammation via Activation of GPR37 in Macrophages

by Zhengjiang Qian, Chunhua Liu, Hongchao Li, Haiyang Yang, Jianhao Wu, Jing Liu, Yanjiao Li, Xuhui Chen, Jianyang Xu and Xiang Li

Biomedicines 2022, 10(5), 1006; https://doi.org/10.3390/biomedicines10051006 - 27 Apr 2022

Cited by 2 | Viewed by 2209

Abstract

The G protein-coupled receptor 37 (GPR37) has been reported to be expressed in macrophages and the activation of GPR37 by its ligand/agonist, and it can regulate macrophage-associated functions and inflammatory responses. Since our previous work identified that osteocalcin (OCN) acts as an endogenous [...] Read more.

The G protein-coupled receptor 37 (GPR37) has been reported to be expressed in macrophages and the activation of GPR37 by its ligand/agonist, and it can regulate macrophage-associated functions and inflammatory responses. Since our previous work identified that osteocalcin (OCN) acts as an endogenous ligand for GPR37 and can elicit various intracellular signals by interacting with GPR37, we thus hypothesized that OCN may also play a functional role in macrophage through the activation of GPR37. To verify the hypothesis, we conducted a series of in vivo and in vitro studies in lipopolysaccharide (LPS)-challenged mice and primary cultured macrophages. Our results reveal that the OCN gene deletion (OCN^−/−) and wild type (WT) mice showed comparable death rates and inflammatory cytokines productions in response to a lethal dose of LPS exposure. However, the detrimental effects caused by LPS were significantly ameliorated by exogenous OCN treatments in both WT and OCN^−/− mice. Notably, the protective effects of OCN were absent in GPR37^−/− mice. In coordination with the in vivo results, our in vitro studies further illustrated that OCN triggered intracellular responses via GPR37 in peritoneal macrophages by regulating the release of inflammatory factors and macrophage phagocytic function. Finally, we exhibited that the adoptive transfer of OCN-treated macrophages from WT mice significantly inhibits the release of pro-inflammatory cytokines in GPR37^−/− mice exposed to LPS. Taken together, these findings suggest a protective role of OCN against LPS-caused acute inflammation, by the activation of GPR37 in macrophages, and provide a potential application of the activation of the OCN/GPR37 regulatory axis as a therapeutic strategy for inflammatory diseases. Full article

(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 3.0)

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14 pages, 2069 KiB

Open AccessArticle

Raman Microspectroscopy Identifies Biochemical Activation Fingerprints in THP-1- and PBMC-Derived Macrophages

by Nora Feuerer, Daniel A. Carvajal Berrio, Florian Billing, Sören Segan, Martin Weiss, Ulrich Rothbauer, Julia Marzi and Katja Schenke-Layland

Biomedicines 2022, 10(5), 989; https://doi.org/10.3390/biomedicines10050989 - 25 Apr 2022

Cited by 6 | Viewed by 2408

Abstract

(1) The monocytic leukemia cell line THP-1 and primary monocyte-derived macrophages (MDMs) are popular in vitro model systems to study human innate immunity, wound healing, and tissue regeneration. However, both cell types differ significantly in their origin and response to activation stimuli. (2) [...] Read more.

(1) The monocytic leukemia cell line THP-1 and primary monocyte-derived macrophages (MDMs) are popular in vitro model systems to study human innate immunity, wound healing, and tissue regeneration. However, both cell types differ significantly in their origin and response to activation stimuli. (2) Resting THP-1 and MDMs were stimulated with lipopolysaccharide (LPS) and interferon γ (IFNγ) and analyzed by Raman microspectroscopy (RM) before and 48 h after activation. Raman data were subsequently analyzed using principal component analysis. (3) We were able to resolve and analyze the spatial distribution and molecular composition of proteins, nucleic acids, and lipids in resting and activated THP-1 and MDMs. Our findings reveal that proinflammatory activation-induced significant spectral alterations at protein and phospholipid levels in THP-1. In MDMs, we identified that nucleic acid and non-membrane-associated intracellular lipid composition were also affected. (4) Our results show that it is crucial to carefully choose the right cell type for an in vitro model as the nature of the cells itself may impact immune cell polarization or activation results. Moreover, we demonstrated that RM is a sensitive tool for investigating cell-specific responses to activation stimuli and monitoring molecular changes in subcellular structures. Full article

(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 3.0)

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14 pages, 2595 KiB

Open AccessEditor’s ChoiceArticle

Effects of CB2 Receptor Modulation on Macrophage Polarization in Pediatric Celiac Disease

by Chiara Tortora, Alessandra Di Paola, Maura Argenziano, Mara Creoli, Maria Maddalena Marrapodi, Sabrina Cenni, Carlo Tolone, Francesca Rossi and Caterina Strisciuglio

Biomedicines 2022, 10(4), 874; https://doi.org/10.3390/biomedicines10040874 - 09 Apr 2022

Cited by 23 | Viewed by 2314

Abstract

Celiac Disease (CD) represents an autoimmune disorder triggered by the exposure to gluten in genetically susceptible individuals. Recent studies suggest the involvement of macrophages in CD pathogenesis. Macrophages are immune cells, present as pro-inflammatory classically activated macrophages (M1) or as anti-inflammatory alternatively activated [...] Read more.

Celiac Disease (CD) represents an autoimmune disorder triggered by the exposure to gluten in genetically susceptible individuals. Recent studies suggest the involvement of macrophages in CD pathogenesis. Macrophages are immune cells, present as pro-inflammatory classically activated macrophages (M1) or as anti-inflammatory alternatively activated macrophages (M2). The Cannabinoid Receptor 2 (CB2) has important anti-inflammatory and immunoregulatory properties. We previously demonstrated that a common CB2 functional variant, Q63R, causing CB2 reduced function, is associated with several inflammatory and autoimmune diseases The first aim of this study was to investigate the phenotype of macrophages isolated from peripheral blood of CD patients and CB2 expression. The second aim was to evaluate the effects of CB2 pharmacological modulation on CD macrophage polarization. Moreover, by an in vitro model of “immunocompetent gut” we investigated the role of CD macrophages in inducing intestinal barrier damage and the possibility to restore its functionality modulating their polarization. We found an increased expression of M1 macrophages and a CB2 reduced expression. We also demonstrated CD M1 macrophages in inducing the typical mucosal barrier damage of CD. CB2 stimulation switches macrophage polarization towards the anti-inflammatory M2 phenotype thus reducing inflammation but also limiting the epithelial dysfunction. Therefore, we suggest CB2 receptor as a possible novel therapeutic target for CD by regulating macrophages polarization and by preventing mucosal barrier damage. Full article

(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 3.0)

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22 pages, 42052 KiB

Open AccessArticle

Testicular Macrophages Produce Progesterone De Novo Promoted by cAMP and Inhibited by M1 Polarization Inducers

by Sawako Yamauchi, Kousuke Yamamoto and Kazushige Ogawa

Biomedicines 2022, 10(2), 487; https://doi.org/10.3390/biomedicines10020487 - 18 Feb 2022

Cited by 6 | Viewed by 2190

Abstract

Tissue-resident macrophages (Mø) originating from fetal precursors are maintained via self-renewal under tissue-/organ-specific microenvironments. Herein, we developed a propagation method of testicular tissue-resident Mø in mixed primary culture with interstitial cells composed of Leydig cells from the mouse testis. We examined Mø/monocyte marker [...] Read more.

Tissue-resident macrophages (Mø) originating from fetal precursors are maintained via self-renewal under tissue-/organ-specific microenvironments. Herein, we developed a propagation method of testicular tissue-resident Mø in mixed primary culture with interstitial cells composed of Leydig cells from the mouse testis. We examined Mø/monocyte marker expression in propagated testicular Mø using flow cytometry; gene expression involved in testosterone production as well as spermatogenesis in testicular Mø and interstitial cells propagated by mixed culture via RT-PCR; and progesterone (P4) de novo production in propagated testicular Mø treated with cyclic adenosine monophosphate, isoproterenol, and M1 polarization inducers using ELISA. Mø marker expression patterns in the propagated Mø were identical to those in testicular interstitial Mø with a CD206-positive/major histocompatibility complex (MHC) II-negative M2 phenotype. We identified the genes involved in P4 production, transcription factors essential for steroidogenesis, and androgen receptors, and showed that P4 production de novo was upregulated by cyclic adenosine monophosphate and β2-adrenergic stimulation and was downregulated by M1 polarization stimulation in Mø. We also demonstrated the formation of gap junctions between Leydig cells and interstitial Mø. This is the first study to demonstrate de novo P4 production in tissue-resident Mø. Based on previous studies revealing inhibition of testosterone production by P4, we propose that local feedback machinery between Leydig cells and adjacent interstitial Mø regulates testosterone production. The results presented in this study can facilitate future studies on immune-endocrine interactions in gonads that are related to infertility and hormonal disorders. Full article

(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 3.0)

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15 pages, 4563 KiB

Open AccessEditor’s ChoiceArticle

Puerarin Attenuates Obesity-Induced Inflammation and Dyslipidemia by Regulating Macrophages and TNF-Alpha in Obese Mice

by Ji-Won Noh, Hee-Kwon Yang, Min-Soo Jun and Byung-Cheol Lee

Biomedicines 2022, 10(1), 175; https://doi.org/10.3390/biomedicines10010175 - 14 Jan 2022

Cited by 14 | Viewed by 2548

Abstract

Obesity causes low-grade inflammation that results in dyslipidemia and insulin resistance. We evaluated the effect of puerarin on obesity and metabolic complications both in silico and in vivo and investigated the underlying immunological mechanisms. Twenty C57BL/6 mice were divided into four groups: normal [...] Read more.

Obesity causes low-grade inflammation that results in dyslipidemia and insulin resistance. We evaluated the effect of puerarin on obesity and metabolic complications both in silico and in vivo and investigated the underlying immunological mechanisms. Twenty C57BL/6 mice were divided into four groups: normal chow, control (HFD), HFD + puerarin (PUE) 200 mg/kg, and HFD + atorvastatin (ATO) 10 mg/kg groups. We examined bodyweight, oral glucose tolerance test, serum insulin, oral fat tolerance test, serum lipids, and adipocyte size. We also analyzed the percentage of total, M1, and M2 adipose tissue macrophages (ATMs) and the expression of F4/80, tumor necrosis factor-α (TNF-α), C-C motif chemokine ligand 2 (CCL2), CCL4, CCL5, and C-X-C motif chemokine receptor 4. In silico, we identified the treatment-targeted genes of puerarin and simulated molecular docking with puerarin and TNF, M1, and M2 macrophages based on functionally enriched pathways. Puerarin did not significantly change bodyweight but significantly improved fat pad weight, adipocyte size, fat area in the liver, free fatty acids, triglycerides, total cholesterol, and HDL-cholesterol in vivo. In addition, puerarin significantly decreased the ATM population and TNF-α expression. Therefore, puerarin is a potential anti-obesity treatment based on its anti-inflammatory effects in adipose tissue. Full article

(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 3.0)

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Review

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12 pages, 768 KiB

Open AccessReview

Functional Modulation of Human Macrophages by Secreted Phospholipases A₂: Implications in Cancer

by Maria Rosaria Galdiero, Ilaria Mormile, Francescopaolo Granata, Stefania Loffredo, Aikaterini Detoraki, Francesca Della Casa, Maria Luisa Trocchia, Annagioia Ventrici, Amato de Paulis and Francesca Wanda Rossi

Biomedicines 2022, 10(11), 2763; https://doi.org/10.3390/biomedicines10112763 - 31 Oct 2022

Cited by 3 | Viewed by 1239

Abstract

Cancer-related inflammation has recently emerged as an important component of cancer pathogenesis that is able to promote tumor initiation and progression, and the acquisition of the known hallmark capabilities, including evasion from immunosurveillance. Several soluble and cellular mediators participate in tumor microenvironment formation, [...] Read more.

Cancer-related inflammation has recently emerged as an important component of cancer pathogenesis that is able to promote tumor initiation and progression, and the acquisition of the known hallmark capabilities, including evasion from immunosurveillance. Several soluble and cellular mediators participate in tumor microenvironment formation, leading to cancer initiation and progression. In this view, Tumor-Associated Macrophages (TAMs) are pivotal players and, due to their characteristic plasticity, can acquire a variety of distinct phenotypes and contribute in different ways to the different phases of carcinogenesis. Different stimuli have been shown to modulate macrophage polarization. Secreted phospholipase A₂ enzymes (sPLA₂s) exert multiple biological effects on cancer-related inflammation due to their enzymatic activity and ability to activate inflammatory cells by non-enzymatic mechanisms. Among the different sPLA₂ isoforms, several studies have suggested that group IIA and group X are mainly involved in a wide variety of cancer types. A deeper insight into the molecular mechanisms regulating the link between tumor-infiltrating immune cells and cancer could lead to identifying new prognostic/predictive biomarkers and a broader view of cancer immunotherapy. Full article

(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 3.0)

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19 pages, 718 KiB

Open AccessReview

The Role of Diet in Regulation of Macrophages Functioning

by Yurgita R. Varaeva, Tatiana V. Kirichenko, Nataliya N. Shaposhnikova, Dmitry B. Nikityuk and Antonina V. Starodubova

Biomedicines 2022, 10(9), 2087; https://doi.org/10.3390/biomedicines10092087 - 26 Aug 2022

Cited by 2 | Viewed by 1518

Abstract

The great importance of diet for health and high life-expectancy is established. The impact of nutrients on immune system is a point of growing research interest. Recent studies have found pro- and anti-inflammatory properties of some diet patterns and nutrients that can be [...] Read more.

The great importance of diet for health and high life-expectancy is established. The impact of nutrients on immune system is a point of growing research interest. Recent studies have found pro- and anti-inflammatory properties of some diet patterns and nutrients that can be used from the bench to the bedside for chronic low-grade inflammatory status correction. In this regard, the assessment of potential effects of nutrition on macrophage differentiation, proliferation, and functioning in health and disease is highly demanded. In this review, we present current data on the effects of nutrients on the macrophage functioning. Full article

(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 3.0)

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18 pages, 1601 KiB

Open AccessReview

Functional Phenotypes of Intraplaque Macrophages and Their Distinct Roles in Atherosclerosis Development and Atheroinflammation

by Nataliya V. Mushenkova, Nikita G. Nikiforov, Alexandra A. Melnichenko, Vladislav Kalmykov, Nikolay K. Shakhpazyan, Varvara A. Orekhova and Alexander N. Orekhov

Biomedicines 2022, 10(2), 452; https://doi.org/10.3390/biomedicines10020452 - 15 Feb 2022

Cited by 10 | Viewed by 4193

Abstract

Macrophages are the key inflammatory cell type involved in all stages of atherosclerosis development and progression, as demonstrated by numerous studies. Correspondingly, macrophages are currently regarded as a promising therapeutic target for the development of new treatment approaches. The macrophage population is heterogeneous [...] Read more.

Macrophages are the key inflammatory cell type involved in all stages of atherosclerosis development and progression, as demonstrated by numerous studies. Correspondingly, macrophages are currently regarded as a promising therapeutic target for the development of new treatment approaches. The macrophage population is heterogeneous and dynamic, as these cells can switch between a number of distinct functional states with pro- and anti-atherogenic activity in response to various stimuli. An atherosclerotic plaque microenvironment defined by cytokine levels, cell-to-cell interactions, lipid accumulation, hypoxia, neoangiogenesis, and intraplaque haemorrhage may guide local macrophage polarization processes within the lesion. In this review, we discuss known functional phenotypes of intraplaque macrophages and their distinct contribution to ahteroinflammation. Full article

(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 3.0)

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