scholarly journals C1q/TNF-Related Protein 3 (CTRP-3) Deficiency of Adipocytes Affects White Adipose Tissue Mass but Not Systemic CTRP-3 Concentrations

2021 ◽  
Vol 22 (4) ◽  
pp. 1670
Author(s):  
Andreas Schmid ◽  
Martin Roderfeld ◽  
Jonas Gehl ◽  
Elke Roeb ◽  
Andrea Nist ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Peroxisome Proliferator ◽  
Related Protein ◽  
Tissue Mass ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory ◽  
The Impact

CTRP-3 (C1q/TNF-related protein-3) is an adipokine with endocrine and immunological function. The impact of adipocyte CTRP-3 production on systemic CTRP-3 concentrations and on adipocyte biology is unknown. A murine model of adipocyte CTRP-3 knockout (KO) was established (via the Cre/loxP system). Serum adipokine levels were quantified by ELISA and adipose tissue (AT) gene expression by real-time PCR. Preadipocytes were isolated from AT and differentiated into adipocytes. Comparative transcriptome analysis was applied in adipocytes and liver tissue. Body weight and AT mass were reduced in CTRP-3 KO mice together with decreased serum leptin. In primary cells from visceral AT of KO mice, expression of adiponectin, progranulin, and resistin was induced, while peroxisome proliferator activated receptor γ (PPARγ) was decreased. M1/M2 macrophage polarization markers were shifted to a more anti-inflammatory phenotype. CTRP-3 expression in AT did not contribute to serum concentrations. AT and liver morphology remained unaffected by CTRP-3 KO. Myelin transcription factor 1-like (Myt1l) was identified as a highly upregulated gene. In conclusion, adipocyte CTRP-3 has a role in adipogenesis and AT weight gain whereas adipocyte differentiation is not impaired by CTRP-3 deficiency. Since no effects on circulating CTRP-3 levels were observed, the impact of adipocyte CTRP-3 KO is limited to adipose tissue. Modified AT gene expression indicates a rather anti-inflammatory phenotype.

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.

scholarly journals CXCL16/CXCR6 Axis in Adipocytes Differentiated from Human Adipose Derived Mesenchymal Stem Cells Regulates Macrophage Polarization

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3410
Author(s):  
Seung-Cheol Lee ◽  
Yoo-Jung Lee ◽  
Inho Choi ◽  
Min Kim ◽  
Jung-Suk Sung
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Macrophage Polarization ◽  
Inflammatory Factors ◽  
M2 Macrophage ◽  
M2 Polarization ◽  
Chemokine Ligand ◽  
Anti Inflammatory ◽  
Underlying Mechanisms

Adipocytes interact with adipose tissue macrophages (ATMs) that exist as a form of M2 macrophage in healthy adipose tissue and are polarized into M1 macrophages upon cellular stress. ATMs regulate adipose tissue inflammation by secreting cytokines, adipokines, and chemokines. CXC-motif receptor 6 (CXCR6) is the chemokine receptor and interactions with its specific ligand CXC-motif chemokine ligand 16 (CXCL16) modulate the migratory capacities of human adipose-derived mesenchymal stem cells (hADMSCs). CXCR6 is highly expressed on differentiated adipocytes that are non-migratory cells. To evaluate the underlying mechanisms of CXCR6 in adipocytes, THP-1 human monocytes that can be polarized into M1 or M2 macrophages were co-cultured with adipocytes. As results, expression levels of the M1 polarization-inducing factor were decreased, while those of the M2 polarization-inducing factor were significantly increased in differentiated adipocytes in a co-cultured environment with additional CXCL16 treatment. After CXCL16 treatment, the anti-inflammatory factors, including p38 MAPK ad ERK1/2, were upregulated, while the pro-inflammatory pathway mediated by Akt and NF-κB was downregulated in adipocytes in a co-cultured environment. These results revealed that the CXCL16/CXCR6 axis in adipocytes regulates M1 or M2 polarization and displays an immunosuppressive effect by modulating pro-inflammatory or anti-inflammatory pathways. Our results may provide an insight into a potential target as a regulator of the immune response via the CXCL16/CXCR6 axis in adipocytes.

scholarly journals Rice Bran Oil Attenuates Chronic Inflammation by Inducing M2 Macrophage Switching in High-Fat Diet-Fed Obese Mice

Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 359
Author(s):  
Hyejeong Park ◽  
Seungmin Yu ◽  
Wooki Kim
Keyword(s):  
Adipose Tissue ◽  
Rice Bran ◽  
Rice Bran Oil ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Low Grade ◽  
Obese Mice ◽  
Anti Inflammatory ◽  
Low Grade Inflammation ◽  
Inflammatory Effect

Macrophages are involved in all inflammatory processes from killing pathogens to repairing damaged tissue. In the obese state, macrophages infiltrate into enlarged adipose tissue and polarize into pro-inflammatory M1 macrophages, resulting in chronic low-grade inflammation due to the secretion of inflammatory mediators. Rice bran oil (RBO) is an edible oil containing tocopherols, tocotrienols, and γ-oryzanol. Previous research in normal diet-fed mice suggested that RBO mitigates inflammatory responses by modulating mitochondrial respiration of macrophages. Therefore, we investigated if RBO had an anti-inflammatory effect in diet-induced obese mice by assessing the expression of inflammatory markers in epididymal white adipose tissue (eWAT) and polarization of bone marrow-derived macrophages (BMDMs). Rice bran oil exerted a local anti-inflammatory effect in white adipose tissue by suppressing the production of inflammatory mediators and upregulating transcription of anti-inflammatory genes. Rice bran oil also promoted anti-inflammatory M2 macrophage polarization in BMDMs thereby affecting systemic inflammation. Overall, our in vivo and ex vivo results highlight the potential of RBO as a dietary mediator that can ameliorate obesity-induced chronic low-grade inflammation by mediating the expression of inflammation-related factors and macrophage polarization.

Supramolecular copolymer modified statins-loaded discoidal rHDLs for atherosclerotic anti-inflammatory therapy by cholesterol efflux and M2 macrophage polarization

2021 ◽  
Author(s):  
Qiqi Zhang ◽  
Jianhua He ◽  
Fengfei Xu ◽  
Xinya Huang ◽  
Yanyan Wang ◽  
...  
Keyword(s):  
Essential Role ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Macrophage Phenotype ◽  
Cholesterol Removal ◽  
Atherosclerosis Progression ◽  
Inflammatory Phenotype ◽  
M2 Macrophage Polarization ◽  
Anti Inflammatory ◽  
Inflammatory Macrophage

Foam cells with the pro-inflammatory macrophage phenotype (M1) play an essential role in atherosclerosis progression. Either cellular cholesterol removal or drug intervention was reported to polarize M1 into anti-inflammatory phenotype...

scholarly journals The Impact of the PCSK-9 / VLDL-Receptor Axis on Inflammatory Cell Polarization

2021 ◽  
Author(s):  
Maria Luisa Barcena ◽  
Misael Estepa ◽  
Louis Marx ◽  
Anne Breiter ◽  
Natalie Haritonow ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Macrophage Polarization ◽  
Inflammatory Cells ◽  
Cell Polarization ◽  
Pcsk9 Inhibitors ◽  
Tnf Α ◽  
Inflammatory Phenotype ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
The Impact

Abstract Background: Studies have shown that lipoproteins, including LDL, VLDL, and ApoE2 have an impact on macrophage polarization, important to atherosclerosis progression. PCSK9 is a key mediator regulating the expression of lipoprotein receptors. The present study investigates the effect of the VLDL/VLDL-R axis on mononuclear cell polarization, as well as the role of PCSK9 and PCSK9 inhibitors (PCSK9i) within this network.Methods: Human monocytic THP-1 cells and human monocyte-derived macrophages isolated from PBMC were treated with LPS/IFN-γ to induce a pro-inflammatory phenotype or with IL-4 /IL-13 to induce an anti-inflammatory phenotype. Cells were then subjected to further treatments including VLDL, LDL, PCSK9, PCSK9i, anti-LDL-R; PMA and TSP-1.Results: LPS/IFN-γ treatment promoted a pro-inflammatory state with an increased expression of pro-inflammatory mediators e.g., TNF-α, CD80, and IL-1β. VLDL co-treatment induced a switch of this pro-inflammatory phenotype to an anti-inflammatory phenotype. In pro-inflammatory cells, VLDL significantly decreased the expression of the M1-markers e.g., TNF-α, CD80, and IL-1β. These effects were eliminated by PCSK9 and restored by co-incubation with a PCSK9i. Migration assays demonstrated that pro-inflammatory cells displayed a significantly higher invasive capacity compared to untreated cells or anti-inflammatory cells. Moreover, pro-inflammatory cell chemotaxis was significantly decreased by VLDL-mediated acquisition of the anti-inflammatory phenotype. PCSK9 significantly lessened this VLDL-mediated migration inhibition, which was reversed by the PCSK9i.Conclusion: VLDL promotes macrophage differentiation towards the anti-inflammatory phenotype. PCSK9, via its capacity to inhibit VLDL-R expression, reverses the VLDL-mediated anti-inflammatory switch, thereby promoting a pro-inflammatory phenotype. Thus, anti-PCSK9 therapies may exert pro-inflammatory suppression within the vessel wall.

scholarly journals Gene Expression Profiling of Orbital Adipose Tissue from Patients with Graves’ Ophthalmopathy: A Potential Role for Secreted Frizzled-Related Protein-1 in Orbital Adipogenesis

2005 ◽  
Vol 90 (8) ◽  
pp. 4730-4735 ◽  
Author(s):  
Seema Kumar ◽  
Alexey Leontovich ◽  
Michael J. Coenen ◽  
Rebecca S. Bahn
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Decompression Surgery ◽  
Peroxisome Proliferator ◽  
Related Protein ◽  
Adipose Tissues ◽  
Graves Ophthalmopathy ◽  
Normal Individuals

Context: The signs and symptoms of Graves’ ophthalmopathy (GO) result from inflammation and increased volume of the orbital adipose tissues and extraocular muscles. Objective: Our objective was to identify differentially regulated genes that may be involved in stimulating the orbital adipose tissue expansion seen in GO. Design: Gene expression profiling was used to compare genes expressed in orbital adipose tissues from GO patients and normal individuals. Setting: The study took place at a private practice tertiary referral center. Patients: Orbital adipose tissues were collected at transantral orbital decompression surgery from 20 euthyroid patients undergoing this procedure for severe GO and at early autopsy from eight normal individuals having no evidence of thyroid or ocular disease. Results: Of the 12,686 genes analyzed, 25 known genes were increased in expression (>4-fold) in GO orbital tissues, whereas 11 genes were decreased (>4-fold). Up-regulated genes, confirmed by quantitative RT-PCR, included secreted frizzled-related protein-1 (sFRP-1; 18.5-fold) and several adipocyte-related genes, including peroxisome proliferator activated receptor-γ (44.1-fold) and adiponectin (25-fold). Treatment in vitro of GO orbital preadipocytes with recombinant sFRP-1 (100 nm) significantly increased adiponectin (2.0-fold; P < 0.05), leptin (7-fold; P < 0.002), and TSH receptor mRNA (13-fold; P < 0.003) levels and enhanced Oil red-O staining in the cultures. Conclusions: These results support the concept that orbital adipogenesis is enhanced in GO and suggest that elevated levels of sFRP-1 in the GO orbit may be involved in stimulating this pathogenic process.

scholarly journals Proteoglycan-4 is an Essential Regulator of Synovial Macrophage Polarization and Inflammatory Macrophage Joint Infiltration

2021 ◽  
Author(s):  
Marwa Qadri ◽  
Gregory D. Jay ◽  
Ling X. Zhang ◽  
Tannin A. Schmidt ◽  
Jennifer Totonchy ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Polarization Spectrum ◽  
Membrane Thickness ◽  
Type I ◽  
Synovial Hyperplasia ◽  
Arginase 1 ◽  
Liposomal Clodronate ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory ◽  
The Impact

Abstract Background: Synovial macrophages (SMs) perform a multitude of functions that include clearance of cell debris and foreign bodies, tissue immune surveillance, and resolution of inflammation. At one end of the macrophage polarization spectrum is the inflammatory phenotype (M1), which secretes IL-1β, IL-6 and expresses iNOS. On the opposite end of the spectrum is the anti-inflammatory phenotype (M2) which is characterized by the secretion of IL-10 and TGF-β. PRG4 is an important regulator of synovial hyperplasia and fibrotic remodeling and the involvement of SM activation in PRG4’s homeostatic role is yet to be defined. Our objectives were to study PRG4’s importance to SM homeostasis, M1 and M2 polarization and joint infiltration of bone marrow-derived macrophages (BMDMs) and investigate the role of SMs in mediating synovial fibrosis in Prg4 gene-trap (Prg4GT/GT) murine knee joints.Methods: SM phenotyping in Prg4GT/GT and Prg4+/+ joints was performed using flow cytometry and the balance between CD86+/CD206- (M1) and CD86-/CD206+ (M2) SMs was studied as animals aged. Expression of iNOS and IL-6 in CD86+ SMs, arginase-1 in CD206+ SMs and the impact of Prg4 recombination on SM polarization and BMDM infiltration following a TLR2 agonist challenge were determined. Inflammatory SMs were depleted using liposomal clodronate and synovial membrane thickness and expression of fibrotic markers: α-SMA, PLOD2 and collagen type I (COL-I) were assessed using immunohistochemistry.Results: Total macrophages in Prg4GT/GT joints were higher than corresponding age-matched Prg4+/+ joints (p<0.0001) and the percentages of CD86+/CD206- and CD86+/CD206+ SMs increased in Prg4GT/GT joints as animals aged (p<0.0001), whereas the percentage of CD86-/CD206+ SMs decreased (p<0.001). CD86+ SMs expressed iNOS and IL-6 compared to CD86- SMs (p<0.0001) while CD206+ SMs also expressed arginase-1. Prg4 re-expression limited the accumulation of CD86+ SMs, increased CD86-/CD206+ SMs and attenuated BMDM recruitment (p<0.001). Liposomal clodronate reduced inflammatory SMs and in turn reduced synovial hyperplasia, α-SMA, PLOD2 and COL-I expression in the synovium (p<0.0001).Conclusions: SM accumulation in the joint and the balance between inflammatory and anti-inflammatory SM subsets are regulated by PRG4. In the absence of PRG4’s role, the synovium is populated with inflammatory macrophages that drive synovial fibrosis.

scholarly journals The role of macrophage polarization and associated mechanisms in regulating the anti-inflammatory action of acupuncture: a literature review and perspectives

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jiaqi Wang ◽  
Shanshan Lu ◽  
Fuming Yang ◽  
Yi Guo ◽  
Zelin Chen ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Scientific Basis ◽  
M2 Macrophage ◽  
Extrinsic Factors ◽  
Therapeutic Goals ◽  
Tissue Microenvironment ◽  
Inflammatory Conditions ◽  
Cytokine Levels ◽  
Anti Inflammatory ◽  
Inflammatory Action

AbstractAcupuncture is used in the treatment of a variety of inflammatory conditions and diseases. However, the mechanisms of its anti-inflammatory action are complex and have not been systematically investigated. Macrophages are key components of the innate immune system, thus, balancing the M1/M2 macrophage ratio and modulating cytokine levels in the inflammatory environment may be desirable therapeutic goals. Evidence has shown that acupuncture has anti-inflammatory actions that affect multiple body systems, including the immune, locomotory, endocrine, nervous, digestive, and respiratory systems, by downregulating pro-inflammatory M1 and upregulating anti-inflammatory M2 macrophages, as well as by modulating associated cytokine secretion. Macrophage polarization is controlled by the interlocking pathways of extrinsic factors, the local tissue microenvironment, and the neural-endocrine-immune systems. It has been suggested that polarization of T lymphocytes and cytokine secretions resulting in modulation of the autonomic nervous system and the hypothalamic–pituitary–adrenal axis, may be upstream mechanisms of acupuncture-induced macrophage polarization. We further propose that macrophage polarization could be the principal pathway involved in acupuncture immune regulation and provide the scientific basis for the clinical application of acupuncture in inflammatory conditions.

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