scholarly journals Attenuation of Diabetic Nephropathy in Diabetic Mice by Fasudil through Regulation of Macrophage Polarization

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Fajiang Xie ◽  
Jiesen Lei ◽  
Maoxia Ran ◽  
Yan Li ◽  
Li Deng ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Kinase Inhibitor ◽  
Macrophage Polarization ◽  
Critical Role ◽  
Renal Tissue ◽  
The Body ◽  
M2 Macrophage ◽  
Diabetic Mice ◽  
M1 Macrophage ◽  
Anti Inflammatory

Inflammation and fibrosis induced by hyperglycemia are considered to play a critical role in the pathogenesis of diabetic nephropathy. As macrophage polarization may determine the severity and progression of inflammation, regulation of macrophage polarization may be an effective method to treat diabetic complications. Fasudil, a potent Rho-kinase inhibitor, reportedly exhibits anti-inflammatory activity. However, whether fasudil reduces hyperglycemia-induced diabetic nephropathy via regulation of macrophage polarization remains unclear. In this study, we investigate the effect of fasudil on diabetic nephropathy in streptozotocin-induced type 1 diabetic mice. Our data showed that fasudil significantly decreased urinary protein and serum creatinine in diabetic mice, whereas it had no effect on the body weight and blood glucose. We also found increased M1-type macrophages and related proinflammatory cytokines, adverse fibrosis in renal tissue of diabetic mice. Interestingly, treatment of diabetic mice with fasudil increased the number of M2-type macrophages and related anti-inflammatory cytokines, which attenuated renal injury in diabetic mice. Taken together, the results of this study suggest that fasudil could slow the progression of diabetic nephropathy. The possible mechanism might be associated with its induction of M2 macrophage polarization and the reduction of M1 macrophage polarization and inflammation.

scholarly journals The effect of coal-derived humic substances and their silver-containing bionanocomposites on arginine balance in peritoneal macrophages of intact mice

2022 ◽  
Vol 20 (4) ◽  
pp. 71-78
Author(s):  
E. S. Trofimova ◽  
M. V. Zykova ◽  
M. G. Danilets ◽  
A. A. Ligacheva ◽  
E. Yu. Sherstoboev ◽  
...  
Keyword(s):  
Humic Substances ◽  
Chronic Wounds ◽  
Macrophage Polarization ◽  
Antigen Presenting Cells ◽  
Peritoneal Macrophages ◽  
Research Area ◽  
The Body ◽  
M1 Macrophage ◽  
Anti Inflammatory ◽  
Antigen Presenting

Background. Antigen-presenting cells (APCs), especially macrophages, play an important role in the body defense against various pathogens. Their dysfunction and polarization are associated with most inflammatory and autoimmune diseases. The inflammatory process is regulated by activation and / or inhibition of genes differentially expressed by macrophages. Successful correction of inflammation leads firstly to elimination of inflammatory stimuli and then to remodeling and restoration of tissues and organs. It was experimentally confirmed that silvercontaining bionanocomposites based on natural humic substances (HS) obtained from coal of different origin, as well as initial matrices of these HS, are capable of activating pro- and anti-inflammatory properties of macrophages.Aim. To study cytotoxic, pyrogenic, and immunomodulatory properties (arginine balance) of initial HS samples and samples of silver nanoparticles ultradispersed in these HS matrices (HS-AgNPs) in the cell culture of peritoneal macrophages, as well as their effect on pro- and anti-inflammatory properties of APCs.Materials and methods. Cultural and biochemical methods were used in the study.Results. The study showed that the samples CHE-K, CHE-AgNPs, CHS-K, and CHP-K increased M1 macrophage polarization due to stimulation of the NO-synthase activity and inhibition of arginase. The samples CHI-K, CHIAgNPs, CHP-AgNPs, and CHS-AgNPs modulated an alternative M2 or M2-like state of macrophage activation. At the same time, HS are not cytotoxic at effective concentrations, and three out of four studied samples did not contain pyrogenic impurities.Conclusion. The use of HS and their silver-containing bionanocomposites, which have the ability to greatly affect the polarization of antigen-presenting cells, is a promising research area in correction of the inflammatory response for solving an important social and medical problem of treating chronic wounds. 

scholarly journals Anti-Inflammatory Effect of Curcumin on the Mouse Model of Myocardial Infarction through Regulating Macrophage Polarization

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Shaoxi Yan ◽  
Mo Zhou ◽  
Xiaoyun Zheng ◽  
Yuanyuan Xing ◽  
Juan Dong ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ventricular Remodeling ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
M1 Macrophages ◽  
Macrophage Marker ◽  
M1 Macrophage ◽  
Anti Inflammatory

Inflammation causes tissue damage and promotes ventricular remodeling after myocardial infarction (MI), and the infiltration and polarization of macrophages play an important role in regulating inflammation post-MI. Here, we investigated the anti-inflammatory function of curcumin after MI and studied its relationship with macrophage polarization. In vivo, curcumin not only attenuated ventricular remodeling 3 months after MI but also suppressed inflammation during the first 7 days post-MI. Importantly, the results of qPCR and immunochemistry showed that curcumin decreased M1 (iNOS, CCL2, and CD86) but increased M2 macrophage (Arg1, CD163, and CD206) marker expression in the myocardium of MI mice during the first 7 days post-MI. And flow cytometry analysis indicated that curcumin suppressed M1 (CD45+Gr-1-CD11b+iNOS+ cells) but enhanced M2 macrophage (CD45+Gr-1-CD11b+Arg+ cells) expansion in the myocardium of MI mice during the first 7 days post-MI. In vitro, curcumin decreased LPS/IFNγ-elevated M1 macrophage marker (iNOS and CD86) expression and the proportion of M1 macrophages (iNOS+F4/80+ cells) but increased LPS/IFNγ-suppressed M2 macrophage marker (Arg1 and CD206) expression and the proportion of M2 macrophages (Arg1+F4/80+ cells). In addition, curcumin modulates M1/M2 macrophage polarization partly via AMPK. In conclusion, curcumin suppressed the MI-induced inflammation by modulating macrophage polarization partly via the AMPK 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 Neutrophil-derived extracellular vesicles: proinflammatory trails and anti-inflammatory microvesicles

2019 ◽  
Author(s):  
Young-Jin Youn ◽  
Sanjeeb Shrestha ◽  
Jun-Kyu Kim ◽  
Yu-Bin Lee ◽  
Jee Hyun Lee ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Pi3k Pathway ◽  
M2 Macrophage ◽  
List Type ◽  
Protective Effects ◽  
M1 Macrophage ◽  
M2 Macrophage Polarization ◽  
Anti Inflammatory

SUMMARYExtracellular vesicles (EVs) are membrane-derived vesicles that mediate intercellular communications. Neutrophils produce different subtypes of EVs during inflammatory responses. Neutrophil-derived trails (NDTRs) are generated by neutrophils migrating toward inflammatory foci, whereas neutrophil-derived microvesicles (NDMVs) are thought to be generated by neutrophils that have arrived at the inflammatory foci. However, the physical and functional characteristics of neutrophil-derived EVs are incompletely understood. In this study, we investigated the similarities and differences between neutrophil-derived EV subtypes. Neutrophil-derived EVs shared similar characteristics regarding stimulators, generation mechanisms, and surface marker expression. Both neutrophil-derived EV subtypes exhibited similar functions, such as direct bactericidal activity and induction of monocyte chemotaxis via MCP-1. However, NDTR generation was dependent on the integrin signaling, while NDMV generation was dependent on the PI3K pathway. The CD16 expression level differentiated the neutrophil-derived EV subtypes. Interestingly, both subtypes showed different patterns of miRNA expression and were easily phagocytosed by monocytes. NDTRs induced M1 macrophage polarization, whereas NDMVs induced M2 macrophage polarization. Moreover, NDTRs but not NDMVs exerted protective effects against sepsis-induced lethality in a murine sepsis model and pathological changes in a murine chronic colitis model. These results suggest a new insight into neutrophil-derived EV subtypes: proinflammatory NDTRs and anti-inflammatory NDMVs.Key pointsNeutrophil-derived trails are proinflammatory extracellular vesicles that induce M1 macrophage polarization and protect against inflammationNeutrophil-derived microvesicles are anti-inflammatory extracellular vesicles that induce M2 macrophage polarization

scholarly journals The role of macrophage polarization and associated mechanisms in regulating the anti-inflammatory action of acupuncture: a literature review and perspectives

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jiaqi Wang ◽  
Shanshan Lu ◽  
Fuming Yang ◽  
Yi Guo ◽  
Zelin Chen ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Scientific Basis ◽  
M2 Macrophage ◽  
Extrinsic Factors ◽  
Therapeutic Goals ◽  
Tissue Microenvironment ◽  
Inflammatory Conditions ◽  
Cytokine Levels ◽  
Anti Inflammatory ◽  
Inflammatory Action

AbstractAcupuncture is used in the treatment of a variety of inflammatory conditions and diseases. However, the mechanisms of its anti-inflammatory action are complex and have not been systematically investigated. Macrophages are key components of the innate immune system, thus, balancing the M1/M2 macrophage ratio and modulating cytokine levels in the inflammatory environment may be desirable therapeutic goals. Evidence has shown that acupuncture has anti-inflammatory actions that affect multiple body systems, including the immune, locomotory, endocrine, nervous, digestive, and respiratory systems, by downregulating pro-inflammatory M1 and upregulating anti-inflammatory M2 macrophages, as well as by modulating associated cytokine secretion. Macrophage polarization is controlled by the interlocking pathways of extrinsic factors, the local tissue microenvironment, and the neural-endocrine-immune systems. It has been suggested that polarization of T lymphocytes and cytokine secretions resulting in modulation of the autonomic nervous system and the hypothalamic–pituitary–adrenal axis, may be upstream mechanisms of acupuncture-induced macrophage polarization. We further propose that macrophage polarization could be the principal pathway involved in acupuncture immune regulation and provide the scientific basis for the clinical application of acupuncture in inflammatory conditions.

scholarly journals Inflammatory M1-like macrophages polarized by NK-4 undergo enhanced phenotypic switching to an anti-inflammatory M2-like phenotype upon co-culture with apoptotic cells

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Keizo Kohno ◽  
Satomi Koya-Miyata ◽  
Akira Harashima ◽  
Takahiko Tsukuda ◽  
Masataka Katakami ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Macrophage Polarization ◽  
Phenotypic Switching ◽  
Apoptotic Cells ◽  
Phenotypic Switch ◽  
Inflammatory Phase ◽  
M1 Macrophage ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Background NK-4 has been used to promote wound healing since the early-1950s; however, the mechanism of action of NK-4 is unknown. In this study, we examined whether NK-4 exerts a regulatory effect on macrophages, which play multiple roles during wound healing from the initial inflammatory phase until the tissue regeneration phase. Results NK-4 treatment of THP-1 macrophages induced morphological features characteristic of classically-activated M1 macrophages, an inflammatory cytokine profile, and increased expression of the M1 macrophage-associated molecules CD38 and CD86. Interestingly, NK-4 augmented TNF-α production by THP-1 macrophages in combination with LPS, Pam3CSK4, or poly(I:C). Furthermore, NK-4 treatment enhanced THP-1 macrophage phagocytosis of latex beads. These results indicate that NK-4 drives macrophage polarization toward an inflammatory M1-like phenotype with increased phagocytic activity. Efferocytosis is a crucial event for resolution of the inflammatory phase in wound healing. NK-4-treated THP-1 macrophages co-cultured with apoptotic Jurkat E6.1 (Apo-J) cells switched from an M1-like phenotype to an M2-like phenotype, as seen in the inverted ratio of TNF-α to IL-10 produced in response to LPS. We identified two separate mechanisms that are involved in this phenotypic switch. First, recognition of phosphatidylserine molecules on Apo-J cells by THP-1 macrophages downregulates TNF-α production. Second, phagocytosis of Apo-J cells by THP-1 macrophages and activation of PI3K/Akt signaling pathway upregulates IL-10 production. Conclusion It is postulated that the phenotypic switch from a proinflammatory M1-like phenotype to an anti-inflammatory M2-like phenotype is dysregulated due to impaired efferocytosis of apoptotic neutrophils at the wound site. Our results demonstrate that NK-4 improves phagocytosis of apoptotic cells, suggesting its potential as a therapeutic strategy to resolve sustained inflammation in chronic wounds.

scholarly journals Effect of Platelet-Rich Plasma on M1/M2 Macrophage Polarization

2021 ◽  
Vol 22 (5) ◽  
pp. 2336
Author(s):  
Ryoka Uchiyama ◽  
Eriko Toyoda ◽  
Miki Maehara ◽  
Shiho Wasai ◽  
Haruka Omura ◽  
...  
Keyword(s):  
Culture Media ◽  
Platelet Rich Plasma ◽  
Point Of Care ◽  
Macrophage Polarization ◽  
Osteoarthritis Of The Knee ◽  
M2 Macrophage ◽  
Related Factors ◽  
Humoral Factors ◽  
M1 Macrophage ◽  
M2 Macrophage Polarization

Osteoarthritis of the knee (OAK) is a chronic degenerative disease and progresses with an imbalance of cytokines and macrophages in the joint. Studies regarding the use of platelet-rich plasma (PRP) as a point-of-care treatment for OAK have reported on its effect on tissue repair and suppression of inflammation but few have reported on its effect on macrophages and macrophage polarization. Based on our clinical experience with two types of PRP kits Cellaid Serum Collection Set P type kit (leukocyte-poor-PRP) and an Autologous Protein Solution kit (APS leukocyte-rich-PRP), we investigated the concentrations of humoral factors in PRPs prepared from the two kits and the effect of humoral factors on macrophage phenotypes. We found that the concentrations of cell components and humoral factors differed between PRPs purified using the two kits; APS had a higher concentration of M1 and M2 macrophage related factors. The addition of PRP supernatants to the culture media of monocyte-derived macrophages and M1 polarized macrophages revealed that PRPs suppressed M1 macrophage polarization and promoted M2 macrophage polarization. This research is the first to report the effect of PRPs purified using commercial kits on macrophage polarization.

847 Inflammasome activation in M2 macrophage restrain the immune suppressive function

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A900-A900
Author(s):  
Ronghua Zhang ◽  
Tienan Wang ◽  
Qing Lin
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Culture System ◽  
Cell Activation ◽  
Macrophage Polarization ◽  
Inflammasome Activation ◽  
M2 Macrophage ◽  
M1 Macrophage ◽  
Suppressive Phenotype

BackgroundMacrophage is an important component in tumor microenvironment (TME) and plays multiple roles in tumor initiation, progression and metastases. In response to various stimuli within TME, macrophage exhibits high level of functional heterogeneity. There are two distinct groups of macrophages: M1 macrophage exhibits pro-inflammatory phenotype with high levels of TNF-a, IL-6, and IL-1ß, while M2 macrophage displays immune suppressive phenotype with high levels of anti-inflammatory cytokines such as IL-10 and TGF-ß. In response to the M2 cytokines, myeloid cells within the TME further acquire higher expression of PD-L1 and thus inactivate T cells. M2 cytokines can also directly inhibit T cell activation. As a result, re-polarizing M2 macrophages becomes a key concept for cancer immunotherapy. The NLRP3 inflammasome is acquired by macrophages to fight against endogenous danger signals. Macrophage NLRP3 activation has been observed in several tumor models, but the function of NLRP3 on macrophage polarity remains controversial. Inflammasome activation with IL-1ß/IL-18 secretion was reported to promote M1 polarization. However, NLRP3 activation was also reported to promote M2 polarity through up-regulation of IL4 in asthma modelMethodsHere, we have established an in vitro human macrophage NLRP3 activation system (figure 1), coupled with M2 macrophage polarization assay, to dissect the role of NLRP3 in macrophage phenotype.ResultsOur results indicate that NLRP3 activation restrained M2 phenotype and further enhanced T cell activation in an M2/T cell co-culture system (figure 2).Abstract 847 Figure 1Inflammasome activation polarize M2 macrophage intUse LPS/ATP to stimulate NLRP3 in M2 macrophage and demonstrate NLRP3 activation could reduce CD163 and increase CD86Abstract 847 Figure 2Inflammasome in M2 rescue T cell activationestablish M2/T co-culture system in vitro to demonstrate M2 could suppress T activation while Inflammatory M2 could partial rescue the suppressive phenotypeConclusionsInflammasome could be the potential target for cancer by modulating T cell activation through macrophage polarization regulation

scholarly journals Eplerenone prevented obesity-induced inflammasome activation and glucose intolerance

2017 ◽  
Vol 235 (3) ◽  
pp. 179-191 ◽  
Author(s):  
Tsutomu Wada ◽  
Akari Ishikawa ◽  
Eri Watanabe ◽  
Yuto Nakamura ◽  
Yusuke Aruga ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Intolerance ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
M2 Macrophage ◽  
Expression Levels ◽  
Nlrp3 Inflammasome Activation ◽  
M1 Macrophage ◽  
Anti Inflammatory

Obesity-associated activation of the renin-angiotensin-aldosterone system is implicated in the pathogenesis of insulin resistance; however, influences of mineralocorticoid receptor (MR) inhibition remain unclear. Therefore, we aimed to clarify the anti-inflammatory mechanisms of MR inhibition using eplerenone, a selective MR antagonist, in C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks. Eplerenone prevented excessive body weight gain and fat accumulation, ameliorated glucose intolerance and insulin resistance and enhanced energy metabolism. In the epididymal white adipose tissue (eWAT), eplerenone prevented obesity-induced accumulation of F4/80+CD11c+CD206−-M1-adipose tissue macrophage (ATM) and reduction of F4/80+CD11c−CD206+-M2-ATM. Interestingly, M1-macrophage exhibited lower expression levels of MR, compared with M2-macrophage, in the ATM of eWAT and in vitro-polarized bone marrow-derived macrophages (BMDM). Importantly, eplerenone and MR knockdown attenuated the increase in the expression levels of proIl1b, Il6 and Tnfa, in the eWAT and liver of HFD-fed mice and LPS-stimulated BMDM. Moreover, eplerenone suppressed IL1b secretion from eWAT of HFD-fed mice. To reveal the anti-inflammatory mechanism, we investigated the involvement of NLRP3-inflammasome activation, a key process of IL1b overproduction. Eplerenone suppressed the expression of the inflammasome components, Nlrp3 and Caspase1, in the eWAT and liver. Concerning the second triggering factors, ROS production and ATP- and nigericin-induced IL1b secretion were suppressed by eplerenone in the LPS-primed BMDM. These results indicate that eplerenone inhibited both the priming and triggering signals that promote NLRP3-inflammasome activation. Therefore, we consider MR to be a crucial target to prevent metabolic disorders by suppressing inflammasome-mediated chronic inflammation in the adipose tissue and liver under obese conditions.

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