scholarly journals Melatonin protects against ischemic stroke by modulating microglia/macrophage polarization toward anti‐inflammatory phenotype through STAT3 pathway

2019 ◽  
Vol 25 (12) ◽  
pp. 1353-1362 ◽  
Author(s):  
Zong‐Jian Liu ◽  
Yuan‐Yuan Ran ◽  
Shu‐Yan Qie ◽  
Wei‐Jun Gong ◽  
Fu‐Hai Gao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Macrophage Polarization ◽  
Stat3 Pathway ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

scholarly journals Microvesicles carrying LRP5 induce macrophage polarization to an anti‐inflammatory phenotype

2021 ◽  
Author(s):  
Aureli Luquero ◽  
Gemma Vilahur ◽  
Javier Crespo ◽  
Lina Badimon ◽  
Maria Borrell‐Pages
Keyword(s):  
Macrophage Polarization ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

scholarly journals Comparative Phenotypic and Functional Analyses of the Effects of IL-10 or TGF-β on Porcine Macrophages

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1098
Author(s):  
Tania Carta ◽  
Elisabetta Razzuoli ◽  
Floriana Fruscione ◽  
Susanna Zinellu ◽  
Dionigia Meloni ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Phagocytic Cells ◽  
Mhc Ii ◽  
Tnf Α ◽  
Regulated Expression ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory ◽  
Functional Analyses ◽  
The Impact ◽  
Immunosuppressive Cytokines

Macrophages are phagocytic cells involved in maintaining tissue homeostasis and defense against pathogens. Macrophages may be polarized into different functionally specialized subsets. M2c macrophages arise following stimulation with IL-10 or TGF-β and mediate anti-inflammatory and tissue repair functions. M2c macrophages remain poorly characterized in the pig, thus we investigated the impact of these regulatory cytokines on porcine monocyte-derived macrophages (moMΦ). The phenotype and functionality of these cells was characterized though confocal microscopy, flow cytometry, ELISA, and RT-qPCR. Both cytokines induced CD14 and MHC II DR down-regulation and reduced IL-6, TNF-α, and CD14 expression, suggestive of an anti-inflammatory phenotype. Interestingly, neither IL-10 or TGF-β were able to trigger IL-10 induction or release by moMΦ. Differences between these cytokines were observed: stimulation with IL-10, but not TGF-β, induced up-regulation of both CD16 and CD163 on moMΦ. In addition, IL-10 down-regulated expression of IL-1β and IL-12p40 4h post-stimulation and induced a stronger impairment of moMΦ ability to respond to either TLR2 or TLR4 agonists. Overall, our results provide an overview of porcine macrophage polarization by two immunosuppressive cytokines, revealing differences between IL-10 and TGF-β, and reporting some peculiarity of swine, which should be considered in translational studies.

scholarly journals Wnt/β-catenin signaling regulates lipopolysaccharide-altered polarizations of RAW264.7 cells and alveolar macrophages in mouse lungs

2021 ◽  
Vol 19 ◽  
pp. 205873922110593
Author(s):  
Jiali Yang ◽  
Ying Wang ◽  
Dandan Yang ◽  
Jia Ma ◽  
Shuang Wu ◽  
...  
Keyword(s):  
Alveolar Macrophage ◽  
Alveolar Macrophages ◽  
Macrophage Polarization ◽  
Raw264.7 Cells ◽  
M1 Polarization ◽  
Inflammatory Phenotype ◽  
Inflammatory State ◽  
Anti Inflammatory

Introduction Macrophages are capable of exerting both proinflammatory and anti-inflammatory functions in response to distinct environmental stimuli, by polarizing into classically inflammatory state (M1) and anti-inflammatory phenotype (M2), respectively. The Wnt/β-catenin signaling plays an important role in the tissue homeostasis and immune regulations, including the macrophage polarizations. However, the molecular mechanism of Wnt/β-catenin signaling in regulating alveolar macrophage polarization in an inflammatory state remains unclear. Methods The Wnt/β-catenin signaling-altered phenotypes of murine macrophage-like RAW264.7 cells in vitro and alveolar macrophage in vivo in both of naïve and lipopolysaccharide-induced inflammation states were accessed by immunoblotting and immunostaining assays. Results The activation of Wnt/β-catenin signaling inhibited macrophage M1 polarization, but promoted alternative M2 polarization in murine RAW264.7 cells under a naïve state. Interestingly, in an LPS-induced inflammation condition, the enhanced Wnt/β-catenin activity suppressed both M1 and M2 polarizations in RAW264.7 cells in vitro, and primary alveolar macrophages of LPS-challenged mice in vivo. Molecular analysis further demonstrated an involvement of Stat signing in regulating Wnt/β-catenin signaling-altered polarizations in mouse alveolar macrophages. Conclusion These results suggest a mechanism by which Wnt/β-catenin signaling modulates macrophage polarization in an inflammation state by regulating the Stat signaling pathway.

scholarly journals Cold Atmospheric Pressure Plasma Treatment Modulates Human Monocytes/Macrophages Responsiveness

Plasma ◽  
2018 ◽  
Vol 1 (2) ◽  
pp. 261-276 ◽  
Author(s):  
Letizia Crestale ◽  
Romolo Laurita ◽  
Anna Liguori ◽  
Augusto Stancampiano ◽  
Maria Talmon ◽  
...  
Keyword(s):  
Plasma Treatment ◽  
Macrophage Polarization ◽  
Immune Surveillance ◽  
Atmospheric Pressure Plasma ◽  
Atmospheric Plasma ◽  
Viability Analysis ◽  
Inflammatory Phenotype ◽  
Cold Atmospheric Pressure Plasma ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

Monocytes are involved in innate immune surveillance, establishment and resolution on inflammation, and can polarize versus M1 (pro-inflammatory) or M2 (anti-inflammatory) macrophages. The possibility to control and drive immune cells activity through plasma stimulation is therefore attractive. We focused on the effects induced by cold-atmospheric plasma on human primary monocytes and monocyte-derived macrophages. Monocytes resulted more susceptible than monocyte-derived macrophages to the plasma treatment as demonstrated by the increase in reactive oxygen (ROS) production and reduction of viability. Macrophages instead were not induced to produce ROS and presented a stable viability. Analysis of macrophage markers demonstrated a time-dependent decrease of the M1 population and a correspondent increase of M2 monocyte-derived macrophages (MDM). These findings suggest that plasma treatment may drive macrophage polarization towards an anti-inflammatory phenotype.

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 Exosomes derived from bMSCs inhibit neuroinflammatory after traumatic brain injury by influencing the IL-10/STAT3 signaling pathway

2021 ◽  
Author(s):  
Liang Wen ◽  
Yadong Wang ◽  
Dongfeng Shen ◽  
Peidong Zheng ◽  
Mengdi Tu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Neuronal Apoptosis ◽  
Stat3 Pathway ◽  
Marrow Mesenchymal Stem Cells ◽  
Inflammatory Phenotype ◽  
Microrna Sequencing ◽  
Bv2 Microglia ◽  
Anti Inflammatory

Abstract Exosomes are important membranous vesicles in several physiological and pathological processes. It is postulated that the microRNAs contained in the exosomes play the major roles in these processes. Exosomal microRNAs from bone marrow mesenchymal stem cells (bMSCs) have emerged as promising therapeutic agents against inflammation. However, its specific mechanism has not been clarified. The present study was designed to elucidate the underlying mechanism of bone marrow mesenchymal stem cells derived exosomes on neuroinflammation in vitro and in vivo.Methods: In vitro co-culture experiments were done to demonstrate the effects of bMSCs and bMSCs-derived exosomes on the polarization state of BV2 microglia cells. In vivo experiments were subsequently done to validate the role of exosomes derived from bMSCs in neuro-inflammation after brain injury. MicroRNA sequencing was then done to reveal the potential expanded diversity between bMSCs and exosomes derived from bMSCs. The microRNAs were then screened and quantified by quantitative polymerase chain reaction (qPCR) to identify the most significant miRNAs. Moreover, lentiviral transfection was performed to establish animal models with overexpressed and downregulated microRNA expression levels. The animal models were subsequently used to determine the effects of specific microRNAs on neuroinflammation after TBI and their possible mechanisms of action. Results: Both bMSCs and exosomes derived from bMSCs promoted the polarization of activated BV2 microglia cells to the anti-inflammatory phenotype. They inhibited the expression of pro-inflammatory cytokines but promoted the expression of anti-inflammatory cytokines. Exosomes derived from bMSCs played a stronger role in regulating the expression of inflammatory factors. In vivo animal-based experiments further revealed that the exosomes reduced neuronal apoptosis in the cortical area. They also promoted inhibition of neuroinflammation and transformation of microglia to anti-inflammatory phenotype. In addition, MicroRNA sequencing and subsequent analysis revealed that microRNA-181b was actively involved in the process. Subsequent lentiviral transfection studies revealed that overexpression of miR181b effectively reduced neuronal apoptosis and neuroinflammatory response after traumatic brain injury. Overexpression of microRNA181b also promoted the transformation of microglia to the anti-inflammatory phenotype. These effects were achieved through activation of the IL-10/STAT3 pathway.Conclusion: Exosome derived from bMSCs promotes the polarization of microglia to anti-inflammatory phenotype and inhibit neuroinflammation both in vitro and in vivo. They also reduce neuronal apoptosis and protect damaged brain tissue. The microRNA-181b plays a vital role in this process by activating the IL-10/STAT3 pathway. Our study indicates that IL-10/STAT3 pathway may be involved in neuroinflammatory progression and that up-regulation of the microRNA-181b is a potentially new therapeutic approach for neuroinflammation.

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.

scholarly journals Thiamet G mediates neuroprotection in experimental stroke by modulating microglia/macrophage polarization and inhibiting NF-κB p65 signaling

2016 ◽  
Vol 37 (8) ◽  
pp. 2938-2951 ◽  
Author(s):  
Yating He ◽  
Xiaofeng Ma ◽  
Daojing Li ◽  
Junwei Hao
Keyword(s):  
Ischemic Stroke ◽  
Inflammatory Responses ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Macrophage Polarization ◽  
Neurological Deficits ◽  
Experimental Stroke ◽  
Bv2 Cells ◽  
Anti Inflammatory

Inflammatory responses are accountable for secondary injury induced by acute ischemic stroke (AIS). Previous studies indicated that O-GlcNAc modification (O-GlcNAcylation) is involved in the pathology of AIS, and increase of O-GlcNAcylation by glucosamine attenuated the brain damage after ischemia/reperfusion. Inhibition of β-N-acetylglucosaminidase (OGA) with thiamet G (TMG) is an alternative option for accumulating O-GlcNAcylated proteins. In this study, we investigate the neuroprotective effect of TMG in a mouse model of experimental stroke. Our results indicate that TMG administration either before or after middle cerebral artery occlusion (MCAO) surgery dramatically reduced infarct volume compared with that in untreated controls. TMG treatment ameliorated the neurological deficits and improved clinical outcomes in neurobehavioral tests by modulating the expression of pro-inflammatory and anti-inflammatory cytokines. Additionally, TMG administration reduced the number of Iba1+ cells in MCAO mice, decreased expression of the M1 markers, and increased expression of the M2 markers in vivo. In vitro, M1 polarization of BV2 cells was inhibited by TMG treatment. Moreover, TMG decreased the expression of iNOS and COX2 mainly by suppressing NF-κB p65 signaling. These results suggest that TMG exerts a neuroprotective effect and could be useful as an anti-inflammatory agent for ischemic stroke therapy.

scholarly journals Macrophage polarization is linked to Ca2+-independent phospholipase A2β-derived lipids and cross-cell signaling in mice

2019 ◽  
Vol 61 (2) ◽  
pp. 143-158 ◽  
Author(s):  
Alexander J. Nelson ◽  
Daniel J. Stephenson ◽  
Christopher L. Cardona ◽  
Xiaoyong Lei ◽  
Abdulaziz Almutairi ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Lipid Mediator ◽  
Inflammatory Phenotype ◽  
M1 Phenotype ◽  
Anti Inflammatory ◽  
First Time ◽  
Genotypic Control ◽  
Hydrolysis Of ◽  
Phospholipases A

Phospholipases A2 (PLA2s) catalyze hydrolysis of the sn-2 substituent from glycerophospholipids to yield a free fatty acid (i.e., arachidonic acid), which can be metabolized to pro- or anti-inflammatory eicosanoids. Macrophages modulate inflammatory responses and are affected by Ca2+-independent phospholipase A2 (PLA2)β (iPLA2β). Here, we assessed the link between iPLA2β-derived lipids (iDLs) and macrophage polarization. Macrophages from WT and KO (iPLA2β−/−) mice were classically M1 pro-inflammatory phenotype activated or alternatively M2 anti-inflammatory phenotype activated, and eicosanoid production was determined by ultra-performance LC ESI-MS/MS. As a genotypic control, we performed similar analyses on macrophages from RIP.iPLA2β.Tg mice with selective iPLA2β overexpression in β-cells. Compared with WT, generation of select pro-inflammatory prostaglandins (PGs) was lower in iPLA2β−/−, and that of a specialized pro-resolving lipid mediator (SPM), resolvin D2, was higher; both changes are consistent with the M2 phenotype. Conversely, macrophages from RIP.iPLA2β.Tg mice exhibited an opposite landscape, one associated with the M1 phenotype: namely, increased production of pro-inflammatory eicosanoids (6-keto PGF1α, PGE2, leukotriene B4) and decreased ability to generate resolvin D2. These changes were not linked with secretory PLA2 or cytosolic PLA2α or with leakage of the transgene. Thus, we report previously unidentified links between select iPLA2β-derived eicosanoids, an SPM, and macrophage polarization. Importantly, our findings reveal for the first time that β-cell iPLA2β-derived signaling can predispose macrophage responses. These findings suggest that iDLs play critical roles in macrophage polarization, and we posit that they could be targeted therapeutically to counter inflammation-based disorders.

scholarly journals Lentivirus delivery of IL-10 to promote and sustain macrophage polarization towards an anti-inflammatory phenotype

2014 ◽  
Vol 111 (6) ◽  
pp. 1210-1221 ◽  
Author(s):  
R.M. Boehler ◽  
R. Kuo ◽  
S. Shin ◽  
A.G. Goodman ◽  
M.A. Pilecki ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory
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