MiR‐382‐5p suppresses M1 macrophage polarization and inflammatory response in response to bronchopulmonary dysplasia through targeting CDK8: involving inhibition of STAT1 pathway

2021 ◽  
Author(s):  
Yuanyuan Lv ◽  
Yang Li ◽  
Jiangya Wang ◽  
Mei Li ◽  
Wenhao Zhang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Bronchopulmonary Dysplasia ◽  
Macrophage Polarization ◽  
M1 Macrophage

scholarly journals Uremic toxin indoxyl sulfate promotes proinflammatory macrophage activation by regulation of β-catenin and YAP pathways

2021 ◽  
Author(s):  
Ying Li ◽  
Jing Yan ◽  
Minjia Wang ◽  
Jing Lv ◽  
Fei Yan ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Inflammatory Response ◽  
Macrophage Polarization ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Lps Challenge ◽  
Hla Dr ◽  
M1 Macrophage

AbstractEvidence has been shown that indoxyl sulfate (IS) could impair kidney and cardiac functions. Moreover, macrophage polarization played important roles in chronic kidney disease and cardiovascular disease. IS acts as a nephron-vascular toxin, whereas its effect on macrophage polarization during inflammation is still not fully elucidated. In this study, we aimed to investigate the effect of IS on macrophage polarization during lipopolysaccharide (LPS) challenge. THP-1 monocytes were incubated with phorbol 12-myristate-13-acetate (PMA) to differentiate into macrophages, and then incubated with LPS and IS for 24 h. ELISA was used to detect the levels of TNFα, IL-6, IL-1β in THP-1-derived macrophages. Western blot assay was used to detect the levels of arginase1 and iNOS in THP-1-derived macrophages. Percentages of HLA-DR-positive cells (M1 macrophages) and CD206-positive cells (M2 macrophages) were detected by flow cytometry. IS markedly increased the production of the pro-inflammatory factors TNFα, IL-6, IL-1β in LPS-stimulated THP-1-derived macrophages. In addition, IS induced M1 macrophage polarization in response to LPS, as evidenced by the increased expression of iNOS and the increased proportion of HLA-DR+ macrophages. Moreover, IS downregulated the level of β-catenin, and upregulated the level of YAP in LPS-stimulated macrophages. Activating β-catenin signaling or inhibiting YAP signaling suppressed the IS-induced inflammatory response in LPS-stimulated macrophages by inhibiting M1 polarization. IS induced M1 macrophage polarization in LPS-stimulated macrophages via inhibiting β-catenin and activating YAP signaling. In addition, this study provided evidences that activation of β-catenin or inhibition of YAP could alleviate IS-induced inflammatory response in LPS-stimulated macrophages. This finding may contribute to the understanding of immune dysfunction observed in chronic kidney disease and cardiovascular disease.

scholarly journals GDF3 Protects Mice against Sepsis-Induced Cardiac Dysfunction and Mortality by Suppression of Macrophage Pro-Inflammatory Phenotype

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 120 ◽  
Author(s):  
Lu Wang ◽  
Yutian Li ◽  
Xiaohong Wang ◽  
Peng Wang ◽  
Kobina Essandoh ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Macrophage Polarization ◽  
Endotoxic Shock ◽  
Receptor Protein ◽  
Regulatory Function ◽  
Acute Administration ◽  
M1 Macrophage ◽  
Smad3 Phosphorylation ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

Macrophages are critical for regulation of inflammatory response during endotoxemia and septic shock. However, the mediators underlying their regulatory function remain obscure. Growth differentiation factor 3 (GDF3), a member of transforming growth factor beta (TGF-β) superfamily, has been implicated in inflammatory response. Nonetheless, the role of GDF3 in macrophage-regulated endotoxemia/sepsis is unknown. Here, we show that serum GDF3 levels in septic patients are elevated and strongly correlate with severity of sepsis and 28-day mortality. Interestingly, macrophages treated with recombinant GDF3 protein (rGDF3) exhibit greatly reduced production of pro-inflammatory cytokines, comparing to controls upon endotoxin challenge. Moreover, acute administration of rGDF3 to endotoxin-treated mice suppresses macrophage infiltration to the heart, attenuates systemic and cardiac inflammation with less pro-inflammatory macrophages (M1) and more anti-inflammatory macrophages (M2), as well as prolongs mouse survival. Mechanistically, GDF3 is able to activate Smad2/Smad3 phosphorylation, and consequently inhibits the expression of nod-like receptor protein-3 (NLRP3) in macrophages. Accordingly, blockade of Smad2/Smad3 phosphorylation with SB431542 significantly offsets rGDF3-mediated anti-inflammatory effects. Taken together, this study uncovers that GDF3, as a novel sepsis-associated factor, may have a dual role in the pathophysiology of sepsis. Acute administration of rGDF3 into endotoxic shock mice could increase survival outcome and improve cardiac function through anti-inflammatory response by suppression of M1 macrophage phenotype. However, constitutive high levels of GDF3 in human sepsis patients are associated with lethality, suggesting that GDF3 may promote macrophage polarization toward M2 phenotype which could lead to immunosuppression.

scholarly journals Myeloid-Specific Rictor Deletion Induces M1 Macrophage Polarization and Potentiates In Vivo Pro-Inflammatory Response to Lipopolysaccharide

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e95432 ◽  
Author(s):  
William T. Festuccia ◽  
Philippe Pouliot ◽  
Inan Bakan ◽  
David M. Sabatini ◽  
Mathieu Laplante
Keyword(s):  
Inflammatory Response ◽  
Macrophage Polarization ◽  
M1 Macrophage

scholarly journals Characterizing the Role of Glycogen Synthase Kinase (GSK)-3α/β in Macrophage Polarization and the Regulation of Pro-Atherogenic Pathways

2021 ◽  
Author(s):  
Sarvatit Patel ◽  
Geoff Werstuck
Keyword(s):  
Inflammatory Response ◽  
Cell Viability ◽  
Lipid Accumulation ◽  
Glycogen Synthase ◽  
Macrophage Polarization ◽  
Density Lipoprotein ◽  
Myeloid Cell ◽  
Glycogen Synthase Kinase ◽  
Cellular Mechanisms ◽  
M1 Macrophage

Abstract The molecular and cellular mechanisms that link cardiovascular risk factors to the initiation and progression of atherosclerosis are not understood. Recent findings from our laboratory indicate that endoplasmic reticulum (ER) stress signaling through glycogen synthase kinase (GSK)-3α/β induces pro-atherosclerotic pathways. The objective of this study was to define the specific roles of GSK3α and GSK3β in the activation of pro-atherogenic processes in macrophages. Bone marrow derived macrophages (BMDM) were isolated from low-density lipoprotein receptor knockout (Ldlr-/-) mice and Ldlr-/- mice with myeloid deficiency of GSK3α and/or GSK3β. M1 and M2 macrophages were used to examine functions relevant to the development of atherosclerosis, including polarization, inflammatory response, cell viability, lipid accumulation, migration, and metabolism. GSK3α deficiency impairs M1 macrophage polarization, and reduces the inflammatory response and lipid accumulation, but increases macrophage mobility/migration. GSK3β deficiency promotes M1 macrophage polarization, which further increases the inflammatory response and lipid accumulation, but decreases macrophage migration. Macrophages deficient in both GSK3α and GSK3β exhibit increased cell viability, proliferation, and metabolism. These studies begin to delineate the specific roles of GSK3α and GSK3β in macrophage polarization and function. These data suggest that myeloid cell GSK3α signaling regulates M1 macrophage polarization and pro-atherogenic functions to promote atherosclerosis development.

scholarly journals Propofol inhibits inflammatory response by regulating the miR-494/ Nrdp1 pathway in ICH mice model

2020 ◽  
Author(s):  
Shudong Liu ◽  
Wenyan Li ◽  
Hui Shi ◽  
Ge Tang ◽  
Jiangwei Zhang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Mice Model ◽  
Immune Disease ◽  
Neuroinflammatory Response ◽  
M1 Macrophage ◽  
M2 Macrophage Polarization ◽  
Neuro Protective Effect ◽  
Proinflammatory Factors

Abstract Background: Propofol is an anesthetic agent with neuro-protective effect in neuronal injury. However, the mechanism of propofol in M1 macrophage polarization following ICH has not been well studied. Ubiquitination mediated M1/M2 macrophage polarization plays important roles in pathogenesis of immune disease. The experiment analyzed anti-inflammatory effects of propofol in macrophages following ICH. Methods: In the experiment, macrophages were administrated with erythrocyte lysates, and then miR-494, Nrdp1 and M1 related markers were analyzed. In addition, brain inflammatory response, brain edema, and neurological functions of ICH mice were also assessed. Results: We found that propofol decreased miR-494 levels while increased Nrdp1 levels in macrophages after ICH. We also demonstrated that miR-494 inhibited Nrdp1 expression by directly binding its 3′-untranslated region. MiR-494 attenuated Nrdp1 levels and downstream proinflammatory factors production. Upregulation of Nrdp1 in macrophages significantly decreased M1 macrophage polarization. Conclusion: Taken together, these results suggest that propofol can attenuate the neuroinflammatory response of macrophages after ICH through regulation of the miR-494/Nrdp1 pathway.

scholarly journals Propofol inhibits inflammatory response by regulating the miR-494/ Nrdp1 pathway in ICH mice model

2020 ◽  
Author(s):  
Hui Shi ◽  
Qijiang Xiong ◽  
Zhongyan Huang ◽  
zhao yang
Keyword(s):  
Inflammatory Response ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Mice Model ◽  
Immune Disease ◽  
Neuroinflammatory Response ◽  
M1 Macrophage ◽  
M2 Macrophage Polarization ◽  
Neuro Protective Effect ◽  
Proinflammatory Factors

Abstract Background: Propofol is an anesthetic agent with neuro-protective effect in neuronal injury. However, the mechanism of propofol in M1 macrophage polarization following ICH has not been well studied. Ubiquitination mediated M1/M2 macrophage polarization plays important roles in pathogenesis of immune disease. The experiment analyzed anti-inflammatory effects of propofol in macrophages following ICH. Methods: In the experiment, macrophages were administrated with erythrocyte lysates, and then miR-494, Nrdp1 and M1 related markers were analyzed. In addition, brain inflammatory response, brain edema, and neurological functions of ICH mice were also assessed. Results: We found that propofol decreased miR-494 levels while increased Nrdp1 levels in macrophages after ICH. We also demonstrated that miR-494 inhibited Nrdp1 expression by directly binding its 3′-untranslated region. MiR-494 attenuated Nrdp1 levels and downstream proinflammatory factors production. Upregulation of Nrdp1 in macrophages significantly decreased M1 macrophage polarization. Conclusion: Taken together, these results suggest that propofol can attenuate the neuroinflammatory response of macrophages after ICH through regulation of the miR-494/Nrdp1 pathway.

scholarly journals Macrophage Polarization Related to Crystal Phases of Calcium Phosphate Biomaterials

2021 ◽  
Vol 22 (20) ◽  
pp. 11252
Author(s):  
Linghao Xiao ◽  
Yukari Shiwaku ◽  
Ryo Hamai ◽  
Kaori Tsuchiya ◽  
Keiichi Sasaki ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Inflammatory Response ◽  
Macrophage Polarization ◽  
Ion Concentration ◽  
Crystal Phase ◽  
M2 Macrophage ◽  
M1 Macrophage ◽  
Crystal Phases ◽  
Anti Inflammatory ◽  
Excessive Inflammatory Response

Calcium phosphate (CaP) materials influence macrophage polarization during bone healing. However, the effect of the crystal phase of CaP materials on the immune response of bone remains unclear. In this study, the effect of the crystal phases of CaP materials on the regulation of macrophage polarization was investigated. Human THP-1 cells and mouse RAW 264 cells were cultured with octacalcium phosphate (OCP) and its hydrolyzed form Ca-deficient hydroxyapatite to assess the expression of pro-inflammatory M1 and anti-inflammatory M2 macrophage-related genes. OCP inhibited the excessive inflammatory response and switched macrophages to the anti-inflammatory M2 phenotype, which promoted the expression of the interleukin 10 (IL10) gene. In contrast, HL stimulated an excessive inflammatory response by promoting the expression of pro-inflammatory M1 macrophage-related genes. To observe changes in the microenvironment induced by OCP and HL, inorganic phosphate (Pi) and calcium ion (Ca2+) concentrations and pH value in the medium were measured. The expression of the pro-inflammatory M1 macrophage-related genes (tumor necrosis factor alpha (TNFα) and interlukin 1beta (IL1β)) was closely related to the increase in ion concentration caused by the increase in the CaP dose. Together, these results suggest that the microenvironment caused by the crystal phase of CaP materials may be involved in the immune-regulation capacity of CaP materials.

scholarly journals Effect of antibiotic-induced intestinal dysbacteriosis on bronchopulmonary dysplasia and related mechanisms

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiao Ran ◽  
Yu He ◽  
Qing Ai ◽  
Yuan Shi
Keyword(s):  
Gut Microbiota ◽  
Bronchopulmonary Dysplasia ◽  
Macrophage Polarization ◽  
Survival Rates ◽  
Rrna Gene ◽  
M2 Macrophage ◽  
Inflammatory Reactions ◽  
M1 Macrophage ◽  
Hyperoxia Exposure ◽  
Intestinal Dysbacteriosis

Abstract Background Modification of the gut microbiota by antibiotics may influence the disease susceptibility and immunological responses. Infants in the neonatal intensive care unit (NICU) subjected to frequent antibiotics and oxygen therapies, which may give rise to local and systemic inflammatory reactions and progression of bronchopulmonary dysplasia (BPD). This study aimed to investigate the role of intestinal dysbacteriosis by antibiotic therapy before hyperoxia exposure in the progression of BPD. Methods Mice had been exposed to hyperoxia (85% O2) since postnatal day 3 until day 16 for the BPD model establishment, treated with antibiotics from postnatal day 2 until day 8. Treated mice and appropriate controls were harvested on postnatal day 2 or 10 for 16S rRNA gene sequencing, or postnatal day 17 for assessment of alveolar morphometry and macrophages differentiation. Results Antibiotic-induced intestinal dysbacteriosis before hyperoxia exposure gave rise to deterioration of BPD evidenced by reduced survival rates and alveolarization. Moreover, antibiotic-induced intestinal dysbacteriosis resulted in increased M1 macrophage maker (iNOS) and decreased M2 macrophage maker (Arg-1) levels in lung homogenates. Conclusion Broad-spectrum antibiotic-induced intestinal dysbacteriosis may participate in BPD pathogenesis via alteration of the macrophage polarization status. Manipulating the gut microbiota may potentially intervene the therapy of BPD.

scholarly journals Propofol inhibits inflammatory response by regulating the miR-494/ Nrdp1 pathway in ICH mice model

2020 ◽  
Author(s):  
Shudong Liu ◽  
Wenyan Li ◽  
Hui Shi ◽  
Ge Tang ◽  
Jiangwei Zhang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Mice Model ◽  
Immune Disease ◽  
Neuroinflammatory Response ◽  
M1 Macrophage ◽  
M2 Macrophage Polarization ◽  
Neuro Protective Effect ◽  
Proinflammatory Factors

Abstract Background: Propofol is an anesthetic agent with neuro-protective effect in neuronal injury. However, the mechanism of propofol in M1 macrophage polarization following intracerebral hemorrhage (ICH) has not been well studied. Ubiquitination mediated M1/M2 macrophage polarization plays important roles in pathogenesis of immune disease. The experiment analyzed anti-inflammatory effects of propofol in macrophages following ICH. Methods: In the experiment, macrophages were administrated with erythrocyte lysates, and then miR-494, Neuregulin receptor degradation protein-1 (Nrdp1) and M1 related markers were analyzed. In addition, brain inflammatory response, brain edema, and neurological functions of ICH mice were also assessed. Results: We found that propofol decreased miR-494 levels while increased Nrdp1 levels in macrophages after ICH. We also demonstrated that miR-494 inhibited Nrdp1 expression by directly binding its 3′-untranslated region. MiR-494 attenuated Nrdp1 levels and downstream proinflammatory factors production. Upregulation of Nrdp1 in macrophages significantly decreased M1 macrophage polarization. Conclusion: Taken together, these results suggest that propofol can attenuate the neuroinflammatory response of macrophages after ICH through regulation of the miR-494/Nrdp1 pathway.

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