scholarly journals Polysaccharides from Citrus grandis associate with luteolin relieves chronic pharyngitis by anti-inflammatory via suppressing NF-κB pathway and the polarization of M1 macrophages

2018 ◽  
Vol 32 ◽  
pp. 205873841878059 ◽  
Author(s):  
Xiumei Chen ◽  
Yongfeng Lai ◽  
Xicheng Song ◽  
Jinying Wu ◽  
Li Wang ◽  
...  
Keyword(s):  
Disease Severity ◽  
Macrophage Polarization ◽  
Mannose Receptor ◽  
Interferon Regulatory Factor ◽  
Protective Effects ◽  
Regulatory Factor ◽  
Necrosis Factor Alpha ◽  
Ear Edema ◽  
M1 Macrophage ◽  
Anti Inflammatory

Chronic pharyngitis is characterized as a common inflammation of the pharyngeal mucosa, and anti-inflammatory medications are the common treatment to relieve it. Polysacharides of Citrus grandis L. Osbeck (PCG) and luteolin have been reported to have anti-inflammatory activities. In this study, the protective effects of PCG and luteolin on chronic pharyngitis are evaluated and the underlying mechanisms are explored. PCG and luteolin are administrated to animal models with granuloma, ear edema and chronic pharyngitis and the effects of PCG and luteolin on disease severity are evaluated. We also evaluate the effects of PCG and luteolin on inflammatory cytokine production in macrophages stimulated with lipopolysaccharides (LPS)/interferon-gamma (IFN-γ) and detect the effects of PCG and luteolin on macrophage polarization. Finally, we evaluate the effects of PCG and luteolin on activations of LPS-induced downstream signaling pathways. PCG and luteolin alleviate the disease severity of granuloma, ear edema and chronic pharyngitis. PCG and luteolin suppress the productions of pro-inflammatory cytokines interlukin-6 (IL-6), interlukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) in macrophages. Luteolin promotes macrophage M2 polarization by enhancing expressions of arginase (Arg1) and mannose receptor C type 1 (Mrc1). PCG and luteolin suppress nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and interferon regulatory factor 1 (IRF1), interferon regulatory factor 5 (IRF5) expression. PCG together with luteolin relieves chronic pharyngitis by anti-inflammatory via suppressing NF-κB pathway and the polarization of M1 macrophage.

M2C Polarization by Baicalin Enhances Efferocytosis via Upregulation of MERTK Receptor

2018 ◽  
Vol 46 (08) ◽  
pp. 1899-1914 ◽  
Author(s):  
Yin-Siew Lai ◽  
Renanda Baghaz Dzulhamdhani Surya Putra ◽  
Shin-Peir Aui ◽  
Ko-Tung Chang
Keyword(s):  
Macrophage Polarization ◽  
Chinese Herb ◽  
Interleukin 10 ◽  
Interferon Regulatory Factor ◽  
M2 Macrophage ◽  
Gene Transcript ◽  
Regulatory Factor ◽  
Necrosis Factor Alpha ◽  
Murine Bone Marrow ◽  
Arginase 1

Baicalin is the main active ingredient primary isolated from the Chinese herb, Scutellaria baicalensis Georgi. Although baicalin can induce M2 macrophage polarization, we still do not know the subtype of macrophages polarized by baicalin. In this study, we characterized that murine bone marrow derived macrophages induced by M-CSF can be further polarized into M2C phenotype by baicalin. The signatures of M2C macrophages for mRNA expression like interferon regulatory factor 4 (IRF4), interleukin-10 (IL-10), MERTK and PTX3 were up-regulated. Moreover, we observed the concomitantly decreasing of tumor necrosis factor alpha (TNF-[Formula: see text]), interferon regulatory factor 5 (IRF5), IL-6. In contrast, M2 macrophages polarized by IL-4 increased gene transcript of arginase-1 (Arg-1) and surface marker of CD206 indicates that their identity as M2A rather than M2C subtypes. Interestingly, the phagocytosis as well as efferocytosis activity were significantly enhanced in M2C macrophage polarized by baicalin and these capacities were associated with the expression of MERTK receptor. Finally, we conclude that baicalin induced M2C macrophages polarization with both elevations of efferocytosis and anti-inflammatory activity.

scholarly journals Increased Adipose Tissue Expression of Interferon Regulatory Factor (IRF)-5 in Obesity: Association with Metabolic Inflammation

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1418 ◽  
Author(s):  
Sardar Sindhu ◽  
Reeby Thomas ◽  
Shihab Kochumon ◽  
Ajit Wilson ◽  
Mohamed Abu-Farha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Protein Expression ◽  
Macrophage Polarization ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Metabolic Inflammation ◽  
M1 Macrophage ◽  
Gene And Protein Expression ◽  
Local Expression

Interferon regulatory factor (IRF)-5 is known to be involved in M1 macrophage polarization, however, changes in the adipose expression of IRF5 in obesity and their relationship with the local expression of proinflammatory cytokines/chemokines are unknown. Therefore, IRF5 gene expression was determined in the subcutaneous adipose tissue samples from 53 non-diabetic individuals (6 lean, 18 overweight, and 29 obese), using real-time RT-PCR. IRF5 protein expression was also assessed using immunohistochemistry and/or confocal microscopy. Adipose gene expression of signature immune metabolic markers was also determined and compared with adipose IRF5 gene expression. Systemic levels of C-reactive protein and adiponectin were measured by ELISA. The data show that adipose IRF5 gene (P = 0.008) and protein (P = 0.004) expression was upregulated in obese compared with lean individuals. IRF5 expression changes correlated positively with body mass index (BMI; r = 0.37/P = 0.008) and body fat percentage (r = 0.51/P = 0.0004). In obese, IRF5 changes associated positively with HbA1c (r = 0.41/P = 0.02). A good agreement was found between gene and protein expression of IRF5 in obese subjects (r = 0.65/P = 0.001). IRF5 gene expression associated positively with adipose inflammatory signatures including local expression of TNF-α, IL-6, CXCL8, CCL-2/5, IL-1β, IL-18, CXCL-9/10, CCL7, CCR-1/2/5, TLR-2/7/8/9, IRF3, MyD88, IRAK-1, and inflammatory macrophage markers (P < 0.05). Interestingly, IRF5 gene expression correlated positively with CRP (r = 0.37, P = 0.03) and negatively with adiponectin levels (r = −0.43, P = 0.009). In conclusion, elevated adipose IRF5 expression in obesity concurs with the typical inflammatory signatures, locally and systemically. Hence, the IRF5 upregulation may represent a novel adipose tissue marker for metabolic inflammation.

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 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 Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways

2020 ◽  
Author(s):  
Jiansen Lu ◽  
Hongbo Zhang ◽  
Jianying Pan ◽  
Zhiqiang Hu ◽  
Liangliang Liu ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
In Vitro Study ◽  
Cartilage Degeneration ◽  
Research Society ◽  
Preventive Strategy ◽  
Protective Effects ◽  
Erk Mapk ◽  
M1 Macrophage ◽  
Main Components

Abstract Synovial macrophage polarization and interactions between chondrocytes and macrophages are essential for osteoarthritis (OA) development. The present study determined the role and regulatory mechanisms of fargesin, one of the main components of Magnolia fargesii, in macrophage reprogramming and crosstalk across cartilage and synovium. 10-week-old male C57BL/6 mice were randomly assigned to sham-operated, collagenase-induced OA (CIOA)-operated, or CIOA-operated with intraarticular fargesin treatment groups. Fargesin attenuated articular cartilage degeneration and synovitis, resulting in substantially lower Osteoarthritis Research Society International (OARSI) and synovitis scores. In particular, significantly increased M2 polarization and decreased M1 polarization in synovial macrophages were found in fargesin-treated CIOA mice compared to controls. This was accompanied by down-regulation of IL-6 and IL-1β and upregulation of IL-10 in serum. Although conditioned medium (CM) from the M1 macrophage treated with fargesin reduced the expression of matrix metalloproteinase-13, RUNX2, and type X collagen X in OA cartilage, it had no direct effect on chondrocyte metabolism in an in vitro study. Moreover, fargesin exerted protective effects by suppressing p38/ERK MAPK and p65/NF-κB signaling. This study showed that fargesin switched the polarized phenotypes of macrophages from M1 to M2 subtypes and prevented cartilage degeneration partially by down-regulating p38/ERK MAPK and p65/NF-κB signaling. Targeting macrophage reprogramming or blocking the crosstalk between macrophages and chondrocytes in early OA may be an effective preventive strategy.

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 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 A MicroRNA93–Interferon Regulatory Factor-9–Immunoresponsive Gene-1–Itaconic Acid Pathway Modulates M2-Like Macrophage Polarization to Revascularize Ischemic Muscle

Circulation ◽  
2017 ◽  
Vol 135 (24) ◽  
pp. 2403-2425 ◽  
Author(s):  
Vijay Chaitanya Ganta ◽  
Min Hyub Choi ◽  
Anna Kutateladze ◽  
Todd E. Fox ◽  
Charles R. Farber ◽  
...  
Keyword(s):  
Itaconic Acid ◽  
Macrophage Polarization ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Acid Pathway ◽  
Ischemic Muscle

scholarly journals PICK1 confers anti-inflammatory effects in acute liver injury via suppressing M1 macrophage polarization

Biochimie ◽  
2016 ◽  
Vol 127 ◽  
pp. 121-132 ◽  
Author(s):  
Juan Xie ◽  
Xiaoqin Wu ◽  
Qun Zhou ◽  
Yang Yang ◽  
Yuanyao Tian ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Macrophage Polarization ◽  
M1 Macrophage ◽  
Anti Inflammatory
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