scholarly journals Hypoxic Tumor-Derived Exosomes Induce M2 Macrophage Polarization via AMPK/p38 To Promote Lung Cancer Progression

2021 ◽  
Author(s):  
Shiyu Zhou ◽  
Yu Lan ◽  
Yuqun Li ◽  
Zhenxing Li ◽  
Jinding Pu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Western Blot ◽  
Cancer Progression ◽  
Macrophage Polarization ◽  
A549 Cells ◽  
M2 Macrophage ◽  
Mesenchymal Transition ◽  
M2 Polarization ◽  
M2 Macrophage Polarization ◽  
P38 Pathway

Abstract Background Hypoxia is a major regulator of tumor aggressiveness and metastasis in cancer progression. Exosomes (exos) play an important role in the communication between lung cancer and hypoxic microenvironment. However, the underlying mechanisms are largely undefined. Methods Exos isolated from A549 cells under hypoxia conditions. Transmission electron microscopy and nanoparticle tracking analysis were carried out to characterize exos. CCK-8 assay, flow cytometry, Western blot, wound healing and transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of A549 cells, respectively. The M2 polarization of macrophages was evaluated by RT-qPCR and Western blot analysis. In vivo nude mice model was established to determine the regulatory effect of hypoxia/exos on the progression of lung cancer. Results Hypoxic A549 cell-derived exos (hypoxia/exos) promoted the proliferation and migration, and inhibited the apoptosis in A549 cells. The expression of PKM2 was significantly upregulated in hypoxia/exos. Hypoxic exosomal PKM2 induced M2 polarization of macrophages by activating AMPK/p38 pathway. Co-culture with hypoxia/exos-treated macrophages enhanced the migration, invasion, and epithelial-mesenchymal transition (EMT) in A549 cells. Moreover, treatment with hypoxia/exos facilitated the tumor growth and lung metastasis of A549 cells. Conclusions Our findings reveal that hypoxic exosomal PKM2 induces M2 macrophage polarization via AMPK/p38 pathway, and thus exerts a simulative effect on the growth and metastasis of lung carcinoma.

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 Modulation of M2 macrophage polarization by the crosstalk between Stat6 and Trim24

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Tao Yu ◽  
Shucheng Gan ◽  
Qingchen Zhu ◽  
Dongfang Dai ◽  
Ni Li ◽  
...  
Keyword(s):  
Immune Responses ◽  
Macrophage Activation ◽  
Regulatory Mechanism ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Creb Binding Protein ◽  
Human Macrophages ◽  
M2 Polarization ◽  
M2 Macrophage Polarization ◽  
Negative Regulatory Mechanism

Abstract Stat6 is known to drive macrophage M2 polarization. However, how macrophage polarization is fine-tuned by Stat6 is poorly understood. Here, we find that Lys383 of Stat6 is acetylated by the acetyltransferase CREB-binding protein (CBP) during macrophage activation to suppress macrophage M2 polarization. Mechanistically, Trim24, a CBP-associated E3 ligase, promotes Stat6 acetylation by catalyzing CBP ubiquitination at Lys119 to facilitate the recruitment of CBP to Stat6. Loss of Trim24 inhibits Stat6 acetylation and thus promotes M2 polarization in both mouse and human macrophages, potentially compromising antitumor immune responses. By contrast, Stat6 mediates the suppression of TRIM24 expression in M2 macrophages to contribute to the induction of an immunosuppressive tumor niche. Taken together, our findings establish Stat6 acetylation as an essential negative regulatory mechanism that curtails macrophage M2 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.

FPR2 Participates in Epithelial Ovarian Cancer (EOC) Progression Through RhoA Mediated M2 Macrophage Polarization: An Invitro Experimental Study

2020 ◽  
Author(s):  
Xiaohui Xie ◽  
Juan He ◽  
Yaqiong Liu ◽  
Weiwei Chen ◽  
Kun Shi
Keyword(s):  
Ovarian Cancer ◽  
Western Blot ◽  
Cell Lines ◽  
Macrophage Polarization ◽  
Ectopic Expression ◽  
Ovarian Cancer Cells ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Invasion And Metastasis ◽  
M2 Macrophage Polarization

Abstract Background: In our previous study, we found Formyl peptide receptor 2 (FPR2) promoted the invasion and metastasis of EOC and it could be a prognostic marker for EOC. In this study, we aimed to study the possible mechanism of FPR2 in promoting EOC progression.Methods: The FPR2 ectopic expression and knockdown EOC cell lines as well as their control cell lines were established and the expression change of RhoA in each cell lines was evaluated by RT-qPCR and Western-blot. Wound healing and Transwell assays were performed to detect the migrational ability of EOCs that affected by FPR2 and RhoA. The supernatant of each EOC cell lines were used to co-culture with the macrophages, and tested the M1 and M2 macrophges biomarkers by flow cytometry. THP-1 cell line was also indcued to differentiated to M1 and M2 macrophages, FPR2 and RhoA expression in each macrophage cell lines were detected by RT-qPCR and Western-blot. Results: RhoA expression was significantly increased in EOCs along with the overexpression of FPR2, which showed a positive correlation by Pearson correlation analysis. FPR2 ectopic expression would contribute to the migrational ability of EOCs, and RhoA inhibitor (C3 transferase) would impare EOCs migration. Furthermore, FPR2 stimulated the secretion of Th2 cytokines by EOCs, which induced macrophages differentiate to M2 phenotype, while RhoA inhibitor stimulate the secretion of Th1 cytokines and induce macrophages differentiate to M1 phenotype. Moreover, compared with M1 macrophages and THP-1 cells, FPR2 and RhoA expression were significantly up-regulated in M2 macrophages.Conclusion: FPR2 stimulated M2 macrophage polarization and promote invasion and metastasis of ovarian cancer cells through RhoA.

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