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

scholarly journals MCC950 Ameliorates Acute Liver Injury Through Modulating Macrophage Polarization and Myeloid-Derived Suppressor Cells Function

2021 ◽  
Vol 8 ◽  
Author(s):  
Wei Yan ◽  
Yingchun Shen ◽  
Jinny Huang ◽  
Ling Lu ◽  
Qian Zhang
Keyword(s):  
Liver Injury ◽  
Molecular Mechanisms ◽  
Acute Liver Injury ◽  
Macrophage Polarization ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Pathological Process ◽  
M2 Macrophage ◽  
Pyrin Domain ◽  
M1 Macrophage

Acute liver injury (ALI) raises high mortality rates due to a rapid pathological process. MCC950, a highly selective nod-like receptor family pyrin domain containing 3 (NLRP3) inhibitor, has already been reported to show strong hepatoprotective effects in many different liver diseases. In this study, we unveiled the role of MCC950 in carbon tetrachloride (CCl4)-induced ALI and its underlying molecular mechanisms on days 1, 2, and 3. MCC950 could significantly inhibit liver injury, evidenced by decreased serum alamine aminotransferase (ALT) and aspartate aminotransferase (AST) levels on days 1 and 2, increased Albumin (ALB) level on day 3, and decreased histological score during the whole period. Moreover, lower M1 macrophage related to pro-inflammatory genes expression was observed in MCC950-treated ALI mice on day 1, while MCC950 pretreatment also polarized macrophage to M2 phenotype indicating anti-inflammatory response on days 2 and 3. Additionally, MDSC was significantly increased in blood, liver, and spleen in ALI mice at different time courses. Specifically, upregulated myeloid-derived suppressor cell (MDSC) proportions were found in blood and spleen on days 1 and 2, but showed decreased trend on day 3. However, liver MDSC numbers were increased on days 2 and 3, but no significance on day 1. In conclusion, MCC950 pretreatment alleviates CCl4-induced ALI through enhanced M2 macrophage and MDSC function at different time points of ALI. Further understanding of MCC950 in ALI may be a new potential therapeutic strategy.

scholarly journals Autophagy deficiency promotes M1 macrophage polarization to exacerbate acute liver injury via ATG5 repression during aging

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Rui Liu ◽  
Juanjuan Cui ◽  
Yating Sun ◽  
Wentao Xu ◽  
Ziming Wang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Macrophage Polarization ◽  
Innate Immune ◽  
Proinflammatory Mediators ◽  
Hepatocyte Regeneration ◽  
M1 Macrophage ◽  
M1 Phenotype ◽  
Secretory Phenotype

AbstractAging disrupts the maintenance of liver homeostasis, which impairs hepatocyte regeneration and aggravates acute liver injury (ALI), ultimately leading to the development of acute liver failure (ALF), a systemic inflammatory response, and even death. Macrophages influence the progression and outcome of ALI through the innate immune system. However, it is still unclear how macrophages regulate ALI during aging. The variation in macrophage autophagy with aging and the influence on macrophage polarization and cytokine release were assessed in BMDMs in vitro. Then, after BMDMs subjected to several treatments were intravenously or intraperitoneally injected into mice, thioacetamide (TAA)-induced ALI (TAA-ALI) was established, and its effects on inflammation, injury, and mortality were assessed. We found that aging aggravated the liver injury, along with increases in the levels of proinflammatory mediators, presenting a senescence-associated secretory phenotype (SASP), which promoted macrophage polarization to the M1 phenotype. In addition, autophagy levels decreased significantly in aged mice, which was ascribed to ATG5 repression during aging. Notably, enhancing autophagy levels in aged BMDMs restored macrophage polarization to that observed under young conditions. Finally, autophagy restoration in aged BMDMs enhanced the protective effect against TAA-ALI, similar to M2 macrophages induced by IL-4. Overall, we demonstrated that the influence of aging on macrophage polarization is an important aggravating factor in TAA-ALI, and the autophagy in macrophages is associated with the aging phenotype.

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 The role of non-steroidal anti-inflammatory drugs in acute liver injury.

BMJ ◽  
1992 ◽  
Vol 305 (6858) ◽  
pp. 865-868 ◽  
Author(s):  
L. A. Garcia Rodriguez ◽  
S. Perez Gutthann ◽  
A. M. Walker ◽  
L. Lueck
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

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.

Protective effect of pterostilbene on concanavalin A-induced acute liver injury

2019 ◽  
Vol 10 (11) ◽  
pp. 7308-7314 ◽  
Author(s):  
Jiayan Wu ◽  
Mengmeng Li ◽  
Jingwen He ◽  
Ke Lv ◽  
Meiyan Wang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Protective Effect ◽  
Concanavalin A ◽  
Acute Liver Injury ◽  
Anti Inflammatory

Pterostilbene (PTE) is broadly found in berries and has antioxidant and anti-inflammatory properties.

scholarly journals Identification of Exosome-Like Nanoparticles as a New Bioactive Component in Honey

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 383-383
Author(s):  
Jiujiu Yu
Keyword(s):  
Liver Injury ◽  
Nlrp3 Inflammasome ◽  
Acute Liver Injury ◽  
Medical Science ◽  
The United States ◽  
United States Department ◽  
Bioactive Component ◽  
Medicinal Food ◽  
Anti Inflammatory ◽  
Experimentally Induced

Abstract Objectives To investigate whether honey, as a medicinal food, contain exosome-like nanoparticles (ELNs). Methods Honey was diluted in phosphate-buffered saline and subjected to sequential centrifugation followed by ultracentrifugation. ELNs were obtained from honey. Such ELNs were characterized in detail by electron microscopy analysis and biomolecule omics analysis. The anti-inflammatory functions of these honey-derived ELNs (H-ELNs) were studied in primary macrophages and experimentally induced acute liver injury in mice. Results H-ELNs were membrane-enclosed nanoparticles composed of lipids, proteins, and RNAs. These nanoparticles specifically hindered assembly and activation of the nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome, which is a critical pro-inflammatory enzyme complex in the innate immune system. H-ELNs protected mice from acute inflammation and liver damage in the experimentally induced acute liver injury. microRNA miR-4057 in H-ELNs was found to potently inhibit activation of the NLRP3 inflammasome. Conclusions H-ELNs were identified as a new bioactive component in honey and these nanoparticles demonstrated potent anti-inflammatory function in vitro and in vivo. This finding opens a new avenue for studying honey, a medicinal food since ancient times. Funding Sources This work was supported by the United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA) and the National Institutes of Health (NIH) National Institute for General Medical Science (NIGMS).

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

2020 ◽  
Author(s):  
Keizo Kohno ◽  
Satomi Koya-Miyata ◽  
Akira Harashima ◽  
Takahiko Tsukuda ◽  
Masataka Katakami ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Macrophage Polarization ◽  
Poly I:C ◽  
Phenotypic Switching ◽  
Phenotypic Switch ◽  
Inflammatory Phase ◽  
Macrophage Phagocytosis ◽  
M1 Macrophage ◽  
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-a production by THP-1 macrophages in combination with LPS, Pam3CSK4, or poly(I:C). Furthermore, NK-4 treatment enhanced THP-1 macrophage phagocytosis. 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-a 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-a 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 efferocytosis, suggesting its potential as a therapeutic strategy to resolve sustained inflammation in chronic wounds.

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