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.

Surgical meshes coated with mesenchymal stem cells provide an anti-inflammatory environment by a M2 macrophage polarization

2016 ◽  
Vol 31 ◽  
pp. 221-230 ◽  
Author(s):  
Rebeca Blázquez ◽  
Francisco Miguel Sánchez-Margallo ◽  
Verónica Álvarez ◽  
Alejandra Usón ◽  
Javier G. Casado
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Surgical Meshes ◽  
M2 Macrophage Polarization ◽  
Anti Inflammatory

scholarly journals Extracellular Vesicles Do Not Mediate the Anti-Inflammatory Actions of Mouse-Derived Adipose Tissue Mesenchymal Stem Cells Secretome

2021 ◽  
Vol 22 (3) ◽  
pp. 1375
Author(s):  
María Carmen Carceller ◽  
María Isabel Guillén ◽  
María Luisa Gil ◽  
María José Alcaraz
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Extracellular Vesicles ◽  
Nuclear Factor Κb ◽  
Peritoneal Macrophages ◽  
Toll Like Receptor 4 ◽  
Anti Inflammatory ◽  
Phagocytic Response

Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor-κB activation. Our results demonstrate the anti-inflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV.

scholarly journals Blockade of the Notch Signaling Pathway Promotes M2 Macrophage Polarization to Suppress Cardiac Fibrosis Remodeling in Mice With Myocardial Infarction

2022 ◽  
Vol 8 ◽  
Author(s):  
Zhi Li ◽  
Miao Nie ◽  
Liming Yu ◽  
Dengshun Tao ◽  
Qiang Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cardiac Fibrosis ◽  
Macrophage Polarization ◽  
Notch Signaling Pathway ◽  
Inflammatory Factors ◽  
M2 Macrophage ◽  
M2 Polarization

Myocardial infarction (MI) is regarded as a serious ischemic heart disease on a global level. The current study set out to explore the mechanism of the Notch signaling pathway in the regulation of fibrosis remodeling after the occurrence of MI. First, experimental mice were infected with recombination signal binding protein J (RBP-J) shRNA and empty adenovirus vector, followed by the establishment of MI mouse models and detection of cardiac function. After 4 weeks of MI, mice in the sh-RBP-J group were found to exhibit significantly improved cardiac function relative to the sh-NC group. Moreover, knockdown of RBP-J brought about decreased infarct area, promoted cardiac macrophages M2 polarization, reduced cardiac fibrosis, and further decreased transcription and protein expressions of inflammatory factors and fibrosis-related factors. Furthermore, downregulation of cylindromatosis (CYLD) using si-CYLD reversed the results that knockdown of RBP-J inhibited fibrogenesis and the release of inflammatory factors. Altogether, our findings indicated that the blockade of Notch signaling promotes M2 polarization of cardiac macrophages and improves cardiac function by inhibiting the imbalance of fibrotic remodeling after MI.

scholarly journals MicroRNA-301a inhibition enhances the immunomodulatory functions of adipose-derived mesenchymal stem cells by induction of macrophage M2 polarization

2020 ◽  
Vol 34 ◽  
pp. 205873842096609
Author(s):  
Li-Wen Hsu ◽  
Kuang-Tzu Huang ◽  
Toshiaki Nakano ◽  
King-Wah Chiu ◽  
Kuang-Den Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Macrophage Polarization ◽  
Cell Types ◽  
Prostaglandin E ◽  
M2 Macrophage ◽  
Toll Like Receptor ◽  
Arginase 1 ◽  
Pge2 Concentration ◽  
Non Coding Rnas

MicroRNAs (miRNAs) are a class of short non-coding RNAs that play a significant role in biological processes in various cell types, including mesenchymal stem cells (MSCs). However, how miRNAs regulate the immunomodulatory functions of adipose-derived MSCs (AD-MSCs) remains unknown. Here, we showed that modulation of miR-301a in AD-MSCs altered macrophage polarization. Bone marrow (BM)-derived macrophages were stimulated with LPS (1 μg/ml) and co-cultured with miRNA transfected AD-MSCs for 24 h. The expression of M1 and M2 markers in macrophages was analyzed. Inhibition of miR-301a induced M2 macrophage with arginase-1, CD163, CD206, and IL-10 upregulation. Additionally, toll-like receptor (TLR)-4 mRNA expression in macrophages was downregulated in co-cultures with AD-MSCs transfected with a miR-301a inhibitor. Nitric oxide (NO) in the supernatant of AD-MSC/macrophage co-culture was also suppressed by inhibition of miR-301a in AD-MSCs. We further found that suppression of miR-301a in AD-MSCs increased prostaglandin E2 (PGE2) concentration in the conditioned medium of the co-culture. Taken together, the results of our study indicate that miR-301a can modulate the immunoregulatory functions of AD-MSCs that favor the applicability as a potential immunotherapeutic agent.

scholarly journals Urolithin A, a Gut Metabolite, Induces Metabolic Reprogramming of Adipose Tissue by Promoting M2 Macrophage Polarization and Mitochondrial Function (OR12-02-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Ashley Toney ◽  
Soonkyu Chung
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Function ◽  
Macrophage Polarization ◽  
Peritoneal Macrophages ◽  
M2 Macrophage ◽  
M2 Polarization ◽  
M1 Polarization ◽  
Urolithin A ◽  
M2 Macrophage Polarization

Abstract Objectives Macrophage polarization into pro-inflammatory M1 status is associated with the pathologic progression of adipose remodeling, while M2 polarization is linked with the resolution of inflammation. Urolithin A (UroA) is a gut metabolite derived from ellagic acid found in berries and nuts. Emerging evidence suggests UroA exerts anti-inflammatory function, but the underlying mechanism remains unknown. This study aims to test the hypothesis that UroA attenuates adipose inflammation by promoting M2 macrophage polarization. Methods To investigate the direct role of UroA in vitro, primary bone marrow-derived macrophages (BMDM) were stimulated with LPS for M1 polarization or IL-4/IL-13 for M2 polarization. Oxygen consumption rate was determined in BMDM by Seahorse extracellular flux analyzer. The anti-inflammatory role of UroA is validated by pro-IL-1β Gaussia luciferase (iGLuc) reporter assay and IL-1β secretion in J774 macrophages. Additionally, C57BL/6 mice were fed with a HF diet for 12 weeks along with UroA administration. The M1/M2 polarization status were examined in adipose tissue macrophages (ATM) and peritoneal macrophages by qPCR and protein markers. Results UroA treatment in BMDM in vitro significantly decreased Il-1β (P < 0.001), while increasing M2 markers of Arg1, Ch313 and Mgl2 (P < 0.01). UroA treatment suppressed NLRP3 inflammasome activation in J774 macrophages by decreasing iGLuc activity and IL-1β secretion in a dose-dependent manner. In vivo, UroA administration reduced HF-induced adipocyte hypertrophy, inflammatory markers, and ATM recruitment (P < 0.01) in the adipose tissue. Consistently, UroA suppressed M1 polarization but switched to M2 polarization in peritoneal macrophages, evidenced by decreased M1 signature genes of Cd11c, Tnf-α, Il-6, and Il-1β (P < 0.01), while elevated M2 markers of Ch313 and Mgl2 (P < 0.05). Lastly, UroA not only inhibits HF-driven pathogenic remodeling of adipose tissue, but also promote mitochondrial function and biogenesis. Conclusions UroA attenuates HF-driven pathologic remodeling of adipose tissue by favoring M2 macrophage polarization and augmenting mitochondrial function. Intake of UroA-producing foods may be a promising intervention strategy to mitigate obesity-mediated chronic inflammation and metabolic dysfunction. Funding Sources United States Department of Agriculture National Institute for Food and Agriculture.

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