Autophagy suppresses isoprenaline-induced M2 macrophage polarization via the ROS/ERK and mTOR signaling pathway

Shan, Meihua; Qin, Jianjie; Jin, Fengjiao; Han, Xiao; Guan, Huaijin; Li, Xiaoge; Zhang, Jiahui; Zhang, Hongyao; Wang, Yue

doi:10.1016/j.freeradbiomed.2017.05.021

Cited by 91 publications

(67 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…promote the inflammatory response by suppressing M2 macrophage polarization [33][34][35]. Consequently, we aimed to identify whether Exos from ADSCs have a therapeutic effect on the OGD-induced inflammatory response in primary microglia by promoting autophagy.…”

Section: Cellular Physiology and Biochemistry Cellular Physiology Andmentioning

confidence: 99%

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization

Jiang

Wang

Jin

et al. 2018

Cell Physiol Biochem

242

191

View full text Add to dashboard Cite

Background/Aims: Recent studies have indicated that exosomes secreted from adipose-derived stem cells (ADSCs) have important effects in the treatment of ischemic injury. However, the treatment mechanism is unclear. This study aimed to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-30d-5p have a protective effect on acute ischemic stroke (AIS). Methods: In the current study, inflammatory factors and miR-30d-5p expression were assessed in 70 subjects with AIS and 35 healthy controls. Exosomes were characterized by transmission electron microscopy and further examined using nanoparticle tracking analyses. A rat model of AIS and an in vitro model of oxygen- and glucose-deprived (OGD) primary microglia were established to study the protective mechanism of exosomes from miR-30d-5p-overexpressing ADSCs in ischemia-induced nerve injury. Results: The results showed that following AIS, the expression of inflammatory cytokines increased, while the anti-inflammatory cytokines IL-4, IL-10, and miR-30d-5p decreased both in patients and in animal models. Moreover, in vitro studies demonstrated that suppression of autophagy significantly reduced the OGD-induced inflammatory response. In addition, exosome treatment was more effective in suppressing the inflammatory response by reversing OGD-induced and autophagy-mediated microglial polarization to M1. Furthermore, in vivo studies showed that exosomes derived from ADSCs significantly decreased the cerebral injury area of infarction by suppressing autophagy and promoting M2 microglia/macrophage polarization. Conclusions: Our results suggest that miR-30d-5p-enhanced ADSC-derived exosomes prevent cerebral injury by inhibiting autophagy-mediated microglial polarization to M1.

show abstract

Section: Cellular Physiology and Biochemistry Cellular Physiology Andmentioning

confidence: 99%

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization

Jiang

Wang

Jin

et al. 2018

Cell Physiol Biochem

242

191

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that ISO can promote the expression of HIF-1α in a variety of cells, which was independent of hypoxia-like environment. In our study [46][47][48], we found that HIF-1a mediated the effect of ISO on osteoblasts to enhance the secretion of CXCL12, indicating that HIF-1a signaling of osteoblasts may mediate prostate cancer bone metastasis in response to sympathetic activation. Further studies are needed to explore the mechanism of ISO-induced HIF-1α expression in osteoblasts.…”

Section: Osteoblasts Triggered By Iso Promote Migration and Invasion mentioning

confidence: 57%

β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells

Huang

Zhang

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Chronic stress is well known to promote tumor progression, however, little is known on whether neurotransmitters released after chronic stress induced sympathetic activation regulate the function of osteoblasts to affect migration and invasion of metastatic cancer cells. Methods: First, the changes in migration and invasion ability of prostate cancer cell lines PC-3 and DU145 were assessed by transwell migration assay. PC-3 and DU145 cells proliferation ability were detected by CCK-8, and HIF-1α expression of osteoblasts and the momentous proteins of epithelial-mesenchymal transition (EMT) of PC-3 and DU145 cells were examined by Western blot. Then, an analysis of the main cytokines associated with bone metastasis in osteoblasts and EMT-related biomarkers in PC-3 and DU145 cells was performed by qRT-PCR. Finally, rescue experiment was performed by using HIF-1α siRNA and inhibitor, HIF-1α overexpression plasmid, β2-adrenergic receptor (β2AR) inhibitor, CXCR4 siRNA and inhibitor. Results: In this study, isoproterenol (ISO), a non-selective β-adrenergic receptor (βAR) agonist, used as a pharmacological surrogate of sympathetic nerve activation induced by chronic stress, exhibited no direct effect on migration and invasion of PC-3 and DU145 prostate cancer cells. Whereas, osteoblasts pretreated with ISO promoted EMT and migration as well as invasion of PC-3 and DU145 cells, which was independent of promoting cell proliferation and could be inhibited by β2AR inhibitor. Mechanistically, ISO increased the secretion of CXCL12 via the β2AR-HIF-1α signaling in osteoblasts. Moreover, overexpression of HIF-1α osteoblasts promoted migration and invasion of PC-3 and DU145 cells, which was inhibited by addition of recombinant knockdown of CXCR4 in PC-3 and DU145 cells, and inhibiting CXCL12-CXCR4 signaling with LY2510924 blunted the effects of osteoblasts in response to ISO on EMT and migration as well as invasion of PC-3 and DU145 cells. Conclusions: These findings indicate that β2AR-HIF-1α-CXCL12 signaling in osteoblasts facilitates migration and invasion as well as EMT of prostate cancer cells, and may play a potential role in affecting bone metastasis of prostate cancer.

show abstract

“…Moreover, the role of the mTOR pathway in macrophage activity is involved not only in M1/M2 polarization, but also in processes, such as autophagy, which could indirectly influence the outcome of tumor progression. Indeed, Shan and collaborators demonstrated that rapamycin both reduces the M2 macrophage polarization by down-regulating pSTAT3 on the Tyr705 expression, and increases the autophagy [82]. …”

Section: Immunoregulatory Functions Of Mtormentioning

confidence: 99%

Role of mTOR Signaling in Tumor Microenvironment: An Overview

Cognetti

Bazzichetto

Falcone

et al. 2018

IJMS

112

View full text Add to dashboard Cite

The mammalian target of rapamycin (mTOR) pathway regulates major processes by integrating a variety of exogenous cues, including diverse environmental inputs in the tumor microenvironment (TME). In recent years, it has been well recognized that cancer cells co-exist and co-evolve with their TME, which is often involved in drug resistance. The mTOR pathway modulates the interactions between the stroma and the tumor, thereby affecting both the tumor immunity and angiogenesis. The activation of mTOR signaling is associated with these pro-oncogenic cellular processes, making mTOR a promising target for new combination therapies. This review highlights the role of mTOR signaling in the characterization and the activity of the TME’s elements and their implications in cancer immunotherapy.

show abstract

Autophagy suppresses isoprenaline-induced M2 macrophage polarization via the ROS/ERK and mTOR signaling pathway

Cited by 91 publications

References 38 publications

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization

β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells

Role of mTOR Signaling in Tumor Microenvironment: An Overview

Contact Info

Product

Resources

About