scholarly journals The CDKN2B-AS1/ MIR497/TXNIP axis regulated macrophages

2021 ◽  
Author(s):  
Jianzhong Xu ◽  
Yu Li ◽  
Chenxi Gu ◽  
Guanlei Liu ◽  
Yang Yu
Keyword(s):  
Rheumatoid Arthritis ◽  
Macrophage Polarization ◽  
Critical Role ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Surface Polarization ◽  
M2 Polarization ◽  
M1 Polarization ◽  
Healthy Donors ◽  
And Function

Abstract Abstract The polarization of macrophages plays a critical role in the pathophysiology of rheumatoid arthritis. The polarization states include pro-inflammatory M1 polarization and various alternative anti-inflammatory M2 polarization. Our preliminary results showed that CDKN2B-AS1/MIR497/TXNIP axis might play a role in macrophages extracted from rheumatoid arthritis patients. Therefore, we hypothesized that this axis regulated the polarization of rheumatoid macrophages. Flow cytometry was used to determine the surface polarization markers in M1 or M2 macrophages from healthy donors and rheumatoid arthritis patients. QPCR and western blotting were used to compare the expression of the CDKN2B-AS1/MIR497/TXNIP axis in these macrophages. We interfered with the expression and function of the axis from upstream to downstream in the macrophage cell line MD to test its roles in macrophage polarization. Compared to cells from healthy donors, cells from rheumatoid arthritis patients expressed a higher level of CD40 and CD80 and a lower level of CD16, CD163, CD206, and CD200R after polarization, they also expressed higher CDKN2B-AS1, lower MIR497, and higher TXNIP. In macrophages from healthy donors, there was no correlation among CDKN2B-AS1, MIR497, and TXNIP. But in macrophages patients, they showed significant correlations. The CDKN2B-AS1 knockdown, MIR497 mimics suppressed M1 polarization but promoted M2 polarization in MD cells, while MIR497 knockdown and TXNIP overexpression did the opposite. This study demonstrated that elevated CDKN2B-AS1 in macrophages promotes M1 polarization and inhibits M2 polarization of macrophage by negatively regulating MIR497, thereby upregulated the expression of TXNIP.

scholarly journals Polarization of rheumatoid macrophages is regulated by the CDKN2B-AS1/ MIR497/TXNIP axis

2021 ◽  
Author(s):  
JianZhong Xu
Keyword(s):  
Rheumatoid Arthritis ◽  
Macrophage Polarization ◽  
Critical Role ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Surface Polarization ◽  
M2 Polarization ◽  
M1 Polarization ◽  
Healthy Donors ◽  
And Function

Abstract The polarization of macrophages plays a critical role in the pathophysiology of rheumatoid arthritis. The polarization states include pro-inflammatory M1 polarization and various alternative anti-inflammatory M2 polarization. Our preliminary results showed that CDKN2B-AS1/MIR497/TXNIP axis might play a role in macrophages extracted from rheumatoid arthritis patients. Therefore, we proposed that this axis regulated the polarization of rheumatoid macrophages. Flow cytometry was used to determine the surface polarization markers in M1 or M2 macrophages from healthy donors and rheumatoid arthritis patients. QPCR and western blotting were used to compare the expression of CDKN2B-AS1/MIR497/TXNIP axis in these macrophages. We interfered with the expression and function of the CDKN2B-AS1/ MIR497/TXNIP axis from upstream to downstream in the macrophage cell line MD to test its roles in macrophage polarization. Compared to cells from healthy donors, cells from rheumatoid arthritis patients expressed a higher level of CD40 and CD80 and a lower level of CD16, CD163, CD206, and CD200R after polarization, they also expressed higher CDKN2B-AS1, lower MIR497, and higher TXNIP. In macrophages from healthy donors, there was no correlation among CDKN2B-AS1, MIR497, and TXNIP. But in macrophages patients, they showed significant correlations. The CDKN2B-AS1 knockdown, MIR497 mimics suppressed M1 polarization but promoted M2 polarization in MD cells, while MIR497 knockdown and TXNIP overexpression did the opposite. Elevated CDKN2B-AS1 in macrophages promotes M1 polarization and inhibits M2 polarization of macrophage by negative regulating MIR497, thereby upregulated the expression of TXNIP.

Version up-date: The CDKN2B-AS1/ MIR497/TXNIP axis regulated macrophages

2021 ◽  
Author(s):  
JianZhong Xu
Keyword(s):  
Rheumatoid Arthritis ◽  
Macrophage Polarization ◽  
Critical Role ◽  
M2 Macrophages ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Surface Polarization ◽  
M2 Polarization ◽  
M1 Polarization ◽  
Healthy Donors

Abstract The polarization of macrophages plays a critical role in the pathophysiology of rheumatoid arthritis. The macrophages can have pro-inflammatory M1 polarization and various types of alternative anti-inflammatory M2 polarization. Our preliminary results showed that the CDKN2B-AS1/MIR497/TXNIP axis might regulate macrophages of rheumatoid arthritis patients. Therefore, we hypothesized that this axis regulated the polarization of rheumatoid macrophages. Flow cytometry was used to determine the surface polarization markers in M1 or M2 macrophages from healthy donors and rheumatoid arthritis patients. The QPCR and Western Blotting were used to compare the expression of the CDKN2B-AS1/MIR497/TXNIP axis in these macrophages. We Knocked down and overexpressed the axis in the macrophage cell line MD to test its roles in macrophage polarization. Compared to cells from healthy donors, cells from rheumatoid arthritis patients expressed higher levels of CD40 and CD80 and lower levels of CD16, CD163, CD206, and CD200R after polarization, they also expressed higher CDKN2B-AS1, lower MIR497, and higher TXNIP. In macrophages from healthy donors, there was no correlation among CDKN2B-AS1, MIR497, and TXNIP. But in macrophages from patients, there were significant correlations. The CDKN2B-AS1 knockdown, MIR497 mimics suppressed the M1 polarization but promoted the M2 polarization in MD cells, while the MIR497 knockdown and the TXNIP overexpression did the opposite. This study demonstrated that elevated CDKN2B-AS1 in macrophages promotes the M1 polarization and inhibited the M2 polarization of macrophages by the CDKN2B-AS1/ MIR497/TXNIP axis.

scholarly journals Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiangmei Wang ◽  
Jie Xia ◽  
Ruoqiong Huang ◽  
Yaoqin Hu ◽  
Jiajie Fan ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Macrophage Polarization ◽  
Critical Role ◽  
Cell Contact ◽  
Central Nervous System Diseases ◽  
The Past ◽  
Disease Outcomes ◽  
M2 Polarization ◽  
M1 Polarization

Abstract Mesenchymal stem cells (MSCs) are adult stromal cells that reside in virtually all postnatal tissues. Due to their regenerative and immunomodulatory capacities, MSCs have attracted growing attention during the past two decades. MSC-derived extracellular vesicles (MSC-EVs) are able to duplicate the effects of their parental cells by transferring functional proteins and genetic materials to recipient cells without cell-to-cell contact. MSC-EVs also target macrophages, which play an essential role in innate immunity, adaptive immunity, and homeostasis. Recent studies have demonstrated that MSC-EVs reduce M1 polarization and/or promote M2 polarization in a variety of settings. In this review, we discuss the mechanisms of macrophage polarization and roles of MSC-EV-induced macrophage polarization in the outcomes of cardiovascular, pulmonary, digestive, renal, and central nervous system diseases. In conclusion, MSC-EVs may become a viable alternative to MSCs for the treatment of diseases in which inflammation and immunity play a critical role.

scholarly journals MCP-1 deficiency enhances browning of adipose tissue via increased M2 polarization

2019 ◽  
Vol 242 (2) ◽  
pp. 91-101 ◽  
Author(s):  
Monisha Rajasekaran ◽  
Ok-Joo Sul ◽  
Eun-Kyung Choi ◽  
Ji-Eun Kim ◽  
Jae-Hee Suh ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Nuclear Translocation ◽  
Macrophage Polarization ◽  
Critical Role ◽  
M2 Macrophage ◽  
M2 Polarization ◽  
Mitochondrial Dna Copy Number ◽  
M1 Polarization ◽  
Brown Adipose

Obesity is strongly associated with chronic inflammation for which adipose tissue macrophages play a critical role. The objective of this study is to identify monocyte chemoattractant protein-1 (MCP-1, CCL2) as a key player governing M1–M2 macrophage polarization and energy balance. We evaluated body weight, fat mass, adipocyte size and energy expenditure as well as core body temperature of Ccl2 knockout mice compared with wild-type mice. Adipose tissues, differentiated adipocyte and bone marrow-derived macrophages were assessed by qPCR, Western blot analysis and histochemistry. MCP-1 deficiency augmented energy expenditure by promoting browning in white adipose tissue and brown adipose tissue activity via increasing the expressions of Ucp1, Prdm16, Tnfrsf9, Ppargc1a, Nrf1 and Th and mitochondrial DNA copy number. MCP-1 abrogation promoted M2 polarization which is characterized by increased expression of Arg1, Chil3, Il10 and Klf4 whereas it decreased M1 polarization by decreased p65 nuclear translocation and attenuated expression of Itgax, Tnf and Nos2, leading to increased browning of adipocytes. Enhanced M2 polarization and attenuated M1 polarization in the absence of MCP-1 are independent. Collectively, our results suggest that the action of MCP-1 in macrophages modulates energy expenditure by impairing browning in adipose tissue.

scholarly journals IL-7 and IL-15 combined with strong TCR stimulation decrease Treg suppressive activity in healthy donors and patients with rheumatoid arthritis

2020 ◽  
Author(s):  
Daniil Shevyrev ◽  
Valeriy Tereshchenko ◽  
Alexey Sizikov ◽  
Vladimir Kozlov
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Homeostatic Proliferation ◽  
Suppressive Activity ◽  
Cd8 Cells ◽  
Cell Clones ◽  
Healthy Donors ◽  
Tcr Signals ◽  
And Function

Homeostatic proliferation (HP) is a physiological process to reconstitute the T-cell pool after lymphopenia with IL-7 and IL-15 being the key cytokines regulating the process. However, there is no evidence whether these cytokines influence the function of regulatory T cells (Tregs). Since lymphopenia often accompanies autoimmune diseases, we decided to study the proliferation rate and function of Tregs stimulated by IL-7 and IL-15 in patients with rheumatoid arthritis (RA) compared to healthy donors (HD). The study used peripheral blood from 14 RA patients and 18 HD. Proliferation of purified CD3CD4CD25CD127 cells was assessed by flow cytometry using CFSE. Tregs were stimulated by anti-CD3, IL-7, IL-15, IL-7, or IL-15 combined with anti-CD3, and by IL-2+anti-CD3, and their functional activity was evaluated in each case by CD4 and CD8 cells proliferation inhibition. The suppressive activity of peripheral Tregs did not differ between RA and HD; however, it significantly decreased when IL-7 or IL-15 were applied together with strong TCR stimulation with anti-CD3 antibodies. Herewith Treg proliferation caused by IL-7 and IL-15 was lower in RA than in HD. The revealed decrease in Treg suppressive activity can lead to the proliferation of potentially self-reactive T-cell clones, which can receive relatively strong TCR signals. This may be another explanation of why lymphopenia is associated with the development of autoimmune diseases. The revealed decrease of Treg proliferation under IL-7 and IL-15 may lead to a delay in Treg pool reconstitution in patients with rheumatoid arthritis.

New Aspects of Radiotherapy in Rheumatoid Arthritis Biomarker: Radio Sensitivity Response to Acute Ionizing Radiation Induces Cell Characteristic Reprogramming and Enhanced Cytokine Release of In Vitro Activated Macrophage Cell Line (RAW 264.7)

2021 ◽  
Author(s):  
Zahra Bagheri-Hosseinabadi ◽  
Jaber Zafari ◽  
Fatemeh Javani Jouni ◽  
Hossein Abbasinia ◽  
Mitra Abbasifard
Keyword(s):  
Rheumatoid Arthritis ◽  
Radiation Therapy ◽  
Ionizing Radiation ◽  
Gamma Radiation ◽  
Inflammatory Disease ◽  
Raw 264.7 ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Apoptotic Genes

Abstract The response of biological systems to various types of radiations have many ambiguous dimensions. Among ionizing radiations, in vitro external gamma radiation therapy has mostly studied as model to declare the biological system challenges with radiation effects. Cell/organism exposure to gamma radiation, caused cascade of ionization events such as severe irreversible biological damages. However, the biological responses and oxidative stress related mechanisms under acute radiation conditions poorly understood in inflammatory systems. Following study tried to give a model about ionizing radiation effect on the macrophage that had a key role in inflammation mechanisms; to evaluate the impact of radiotherapy approach for inflammatory disease as rheumatoid arthritis. To this aim, Macrophage cell line (RAW 264.7) culture, exposed to different doses of gamma radiation (0,4, 6, 8, 10 Gy). Cell viability, apoptosis, cell cycle, migration; NO and PGE2 production; expression of pro-inflammatory and apoptotic genes and cytokine secretion of macrophages was also evaluated.The results showed that gamma treatment, at 4 Gy radiation, have slight effect on macrophage characteristics and cytokine secretion pattern. Versus, higher doses (8 and 10 Gy) increased DNA damage, expression of apoptotic genes and secretion of NO and PGE2 cytokines. 6 Gy radiation, the maximum radiation dose, show moderate nondestructive effects and inflammation process modulation. In this study, doses higher than 6 Gy of Gamma radiation caused cell mortality. It seems that 6 Gy Gamma radiation modulate the inflammatory cascade caused by macrophage cell, as a central core of autoimmune inflammatory disease in acute dose radiation therapy.

A core–shell structure QRu-PLGA-RES-DS NP nanocomposite with photothermal response-induced M2 macrophage polarization for rheumatoid arthritis therapy

Nanoscale ◽  
2019 ◽  
Vol 11 (39) ◽  
pp. 18209-18223 ◽  
Author(s):  
Xu Chen ◽  
Xufeng Zhu ◽  
Litao Ma ◽  
Ange Lin ◽  
Youcong Gong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Shell Structure ◽  
Therapeutic Strategy ◽  
Macrophage Polarization ◽  
Core Shell ◽  
M2 Macrophage ◽  
M2 Polarization ◽  
M2 Macrophage Polarization ◽  
Core Shell Structure ◽  
Novel Therapeutic

A novel therapeutic strategy for inducing macrophage M2 polarization by a core–shell QRu-PLGA-RES-DS NPs nanocomposite with photothermal response for RA therapy.

scholarly journals MicroRNA-720 suppresses M2 macrophage polarization by targeting GATA3

2016 ◽  
Vol 36 (4) ◽  
Author(s):  
Yan Zhong ◽  
Chun Yi
Keyword(s):  
Macrophage Polarization ◽  
Ectopic Expression ◽  
Tumour Microenvironment ◽  
M2 Macrophage ◽  
Breast Carcinomas ◽  
Downstream Target ◽  
M2 Polarization ◽  
M2 Macrophage Polarization ◽  
And Function ◽  
M2 Phenotype

Macrophages are highly plastic cells with the ability to differentiate into both M1- and M2-polarized phenotypes. As a distinct M2-polarized population, tumour-associated macrophages (TAMs) promote tumorigenesis owing to their pro-angiogenic and immune-suppressive functions in tumour microenvironment. In the present study, we found that the microRNA-720 (miR-720) was down-regulated in TAMs isolated from breast carcinomas and M2-polarization macrophages. Overexpression of miR-720 attenuated M2 phenotype expression and thus inhibited M2 polarization. We further identified GATA binding protein 3 (GATA3), a transcriptional factor that plays an important role in M2 macrophage polarization, was the downstream target of miR-720. Ectopic expression of GATA3 restored the M2 phenotype in miR-720 overexpressed macrophages. Importantly, overexpression of miR-720 inhibited pro-migration behaviour and phagocytic ability of M2-polarized macrophages. Thus, our data suggest that miR-720 plays an important role in regulating M2 macrophage polarization and function.

scholarly journals AR Deficiency Inhibits LPS-induced M1 Response in Macrophages by Activating Autophagy

2020 ◽  
Author(s):  
Peng Cheng ◽  
Jianwei Xie ◽  
Zhiyong Liu ◽  
Jian Wang
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Critical Role ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
M1 Polarization ◽  
M1 Macrophage ◽  
Oxide Synthase

Abstract Macrophage M1 polarization mediates inflammatory responses and tissue damage. Recently, aldose reductase (AR) has been shown to play a critical role in of M1 polarization in macrophages. However, the underlying mechanisms are unknown. Here, we demonstrated, for the first time, that AR deficiency repressed the induction of inducible nitric oxide synthase in lipopolysaccharide (LPS)-stimulated macrophages via activation of autophagy. This suppression was related to a defect in the inhibitor of nuclear factor κB (NF-κB) kinase (IKK) complex in the classical NF-κB pathway. However, the mRNA levels of the IKKβ and IKKγ were not reduced in LPS-treated AR knockout (KO) macrophages, indicating that their proteins were downregulated at the post-transcriptional level. We discovered that LPS stimuli induced the recruitment of more beclin1 and increased autophagosome formation in AR-deficient macrophages. Blocking autophagy by 3-methyladenine and ammonium chloride treatment restored IKKβ and IKKγ protein levels and increased nitric oxide synthase production in LPS-stimulated AR-deficient macrophages. More assembled IKKβ and IKKγ undergo ubiquitination and recruit the autophagic adaptor p62 in LPS-induced AR KO macrophages, promoting their delivery to autophagosomes and lysosomes. Collectively, these findings suggest that AR deficiency involves in the regulation of NF-κB signaling, and extends the role of selective autophagy in fine-tuned M1 macrophage polarization.

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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