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 Functional delivery of lncRNA TUG1 by endothelial progenitor cells derived extracellular vesicles confers anti-inflammatory macrophage polarization in sepsis via impairing miR-9-5p-targeted SIRT1 inhibition

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Wentao Ma ◽  
Weihong Zhang ◽  
Bing Cui ◽  
Jing Gao ◽  
Qiuhong Liu ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Extracellular Vesicles ◽  
Macrophage Polarization ◽  
Sirtuin 1 ◽  
M2 Macrophage ◽  
Endothelial Progenitor ◽  
M2 Macrophage Polarization ◽  
Anti Inflammatory ◽  
Inflammatory Macrophage

AbstractThe delivery of biomolecules by extracellular vesicles (EVs) derived from endothelial progenitor cells (EPCs) has been proven to ameliorate sepsis, yet the therapeutic mechanism remains to be elucidated. Taurine upregulated gene 1 (TUG1) is a long noncoding RNA (lncRNA) that is downregulated in sepsis. The current study was designed to explore the role of EPCs derived EVs transmitting TUG1 in macrophage polarization and macrophage-mediated inflammation in a cecal ligation and puncture (CLP)-induced sepsis mouse model. TUG1 was underexpressed in CLP-induced sepsis, and its reexpression induced anti-inflammatory macrophage polarization and suppressed macrophage-medicated inflammatory injury to the pulmonary vascular endothelium. EPCs derived EVs transmitted TUG1 to promote M2 macrophage polarization. Luciferase, RIP, and RNA pull-down assays showed that TUG1 could competitively bind to microRNA-9-5p (miR-9-5p) to upregulate the expression of sirtuin 1 (SIRT1). Furthermore, EPCs derived EVs transmitted TUG1 to promote M2 macrophage polarization through the impairment of miR-9-5p-dependent SIRT1 inhibition. Finally, EPCs derived EVs carrying TUG1 were verified to ameliorate sepsis-induced organ damage in the murine model. In summary, EPCs derived EVs transmit TUG1 to attenuate sepsis via macrophage M2 polarization. This study also highlights the proinflammatory mechanism associated with miR-9-5p-mediated inhibition of SIRT1, which contributes to a more comprehensive understanding of the pathogenesis of sepsis.

Immunomodulatory injectable silk hydrogels maintaining functional islets and promoting anti-inflammatory M2 macrophage polarization

Biomaterials ◽  
2018 ◽  
Vol 187 ◽  
pp. 1-17 ◽  
Author(s):  
Manishekhar Kumar ◽  
Prerak Gupta ◽  
Sohenii Bhattacharjee ◽  
Samit K. Nandi ◽  
Biman B. Mandal
Keyword(s):  
Macrophage Polarization ◽  
M2 Macrophage ◽  
M2 Macrophage Polarization ◽  
Anti Inflammatory

scholarly journals M2 Macrophage Polarization Mediates Anti-inflammatory Effects of Endothelial Nitric Oxide Signaling

Diabetes ◽  
2015 ◽  
Vol 64 (8) ◽  
pp. 2836-2846 ◽  
Author(s):  
Woo Je Lee ◽  
Sanshiro Tateya ◽  
Andrew M. Cheng ◽  
Norma Rizzo-DeLeon ◽  
Nicholas F. Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Nitric Oxide Signaling ◽  
M2 Macrophage Polarization ◽  
Anti Inflammatory ◽  
Endothelial Nitric Oxide

scholarly journals EZH1 Is Associated with TCP-Induced Bone Regeneration through Macrophage Polarization

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaoshi Jia ◽  
Hudi Xu ◽  
Richard J. Miron ◽  
Chengcheng Yin ◽  
Xiaoxin Zhang ◽  
...  
Keyword(s):  
Bone Repair ◽  
Macrophage Polarization ◽  
Repair Process ◽  
Potential Interaction ◽  
Target System ◽  
M2 Macrophage ◽  
Macrophage Phenotype ◽  
Gene Target ◽  
M2 Macrophage Polarization ◽  
Antigen Presenting

Macrophages have been found to regulate the effects of biomaterials throughout the entire tissue repair process as an antigen-presenting cell. As a well-defined osteoconductive biomaterial for bone defect regeneration, tricalcium phosphate (TCP) has been found to facilitate a favourable osteoimmunomodulatory response that can shift macrophage polarization towards the M2 phenotype. In the present study, our group discovered that a histone methyltransferase enhancer of zeste1 (EZH1) was drastically downregulated in Thp1 cells stimulated by TCP, indicating that EZH1 may participate in the macrophage phenotype shifting. Furthermore, the NF-κB pathway in macrophages was significantly downregulated through stimulation of TCP, suggesting a potential interaction between EZH1 and the NF-κB pathway. Utilizing gene knock-down therapy in macrophages, it was found that depletion of EZH1 induced M2 macrophage polarization but did not downregulate NF-κB. When the NF-κB pathway was inhibited, the expression of EZH1 was significantly downregulated, suggesting that the inhibition of EZH1 may be regulated by the NF-κB pathway. These novel findings provide valuable insights into a potential gene target system that controls M2 macrophage polarization which ultimately favours a microenvironment suitable for bone repair.

scholarly journals Dehydrocostus Lactone Attenuates Methicillin-Resistant Staphylococcus aureus-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization

2021 ◽  
Vol 22 (18) ◽  
pp. 9754
Author(s):  
Ya-Xian Wu ◽  
Feng-Juan Jiang ◽  
Gang Liu ◽  
Ying-Ying Wang ◽  
Zhi-Qi Gao ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
P38 Mapk ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Gram Positive Bacteria ◽  
M2 Macrophage Polarization ◽  
Anti Inflammatory ◽  
Dehydrocostus Lactone

Dehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the traditional Chinese herbs Saussurea lappa and Inula helenium L., has important anti-inflammatory properties used for treating colitis, fibrosis, and Gram-negative bacteria-induced acute lung injury (ALI). However, the effects of DHL on Gram-positive bacteria-induced macrophage activation and ALI remains unclear. In this study, we found that DHL inhibited the phosphorylation of p38 MAPK, the degradation of IκBα, and the activation and nuclear translocation of NF-κB p65, but enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Nrf2 and HO-1 in lipoteichoic acid (LTA)-stimulated RAW264.7 cells and primary bone-marrow-derived macrophages (BMDMs). Given the critical role of the p38 MAPK/NF-κB and AMPK/Nrf2 signaling pathways in the balance of M1/M2 macrophage polarization and inflammation, we speculated that DHL would also have an effect on macrophage polarization. Further studies verified that DHL promoted M2 macrophage polarization and reduced M1 polarization, then resulted in a decreased inflammatory response. An in vivo study also revealed that DHL exhibited anti-inflammatory effects and ameliorated methicillin-resistant Staphylococcus aureus (MRSA)-induced ALI. In addition, DHL treatment significantly inhibited the p38 MAPK/NF-κB pathway and activated AMPK/Nrf2 signaling, leading to accelerated switching of macrophages from M1 to M2 in the MRSA-induced murine ALI model. Collectively, these data demonstrated that DHL can promote macrophage polarization to an anti-inflammatory M2 phenotype via interfering in p38 MAPK/NF-κB signaling, as well as activating the AMPK/Nrf2 pathway in vitro and in vivo. Our results suggested that DHL might be a novel candidate for treating inflammatory diseases caused by Gram-positive bacteria.

scholarly journals Inhibition of SIK2 and SIK3 during differentiation enhances the anti-inflammatory phenotype of macrophages

2017 ◽  
Vol 474 (4) ◽  
pp. 521-537 ◽  
Author(s):  
Nicola J. Darling ◽  
Rachel Toth ◽  
J. Simon C. Arthur ◽  
Kristopher Clark
Keyword(s):  
Inflammatory Cytokines ◽  
Drug Targets ◽  
Macrophage Polarization ◽  
Macrophage Phenotype ◽  
Integral Role ◽  
Inflammatory Phenotype ◽  
Low Levels ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Pro Inflammatory Cytokines

The salt-inducible kinases (SIKs) control a novel molecular switch regulating macrophage polarization. Pharmacological inhibition of the SIKs induces a macrophage phenotype characterized by the secretion of high levels of anti-inflammatory cytokines, including interleukin (IL)-10, and the secretion of very low levels of pro-inflammatory cytokines, such as tumour necrosis factor α. The SIKs, therefore, represent attractive new drug targets for the treatment of macrophage-driven diseases, but which of the three isoforms, SIK1, SIK2 or SIK3, would be appropriate to target remains unknown. To address this question, we developed knock-in (KI) mice for SIK1, SIK2 and SIK3, in which we introduced a mutation that renders the enzymes catalytically inactive. Characterization of primary macrophages from the single and double KI mice established that all three SIK isoforms, and in particular SIK2 and SIK3, contribute to macrophage polarization. Moreover, we discovered that inhibition of SIK2 and SIK3 during macrophage differentiation greatly enhanced the production of IL-10 compared with their inhibition in mature macrophages. Interestingly, macrophages differentiated in the presence of SIK inhibitors, MRT199665 and HG-9-91-01, still produced very large amounts of IL-10, but very low levels of pro-inflammatory cytokines, even after the SIKs had been reactivated by removal of the drugs. Our data highlight an integral role for SIK2 and SIK3 in innate immunity by preventing the differentiation of macrophages into a potent and stable anti-inflammatory phenotype.

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