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 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 ◽  
Phenotypic Switching ◽  
Apoptotic Cells ◽  
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 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-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 phagocytosis of apoptotic cells, suggesting its potential as a therapeutic strategy to resolve sustained inflammation in chronic wounds.

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.

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 Reviewing the Physiology of Cutaneous Wound Healing and Evaluating the Effect of Exercise on it: A Narrative Review Article

2021 ◽  
Vol 19 (3) ◽  
Author(s):  
Fatima Riyahi ◽  
Simin Riahy ◽  
Mitra Yousefpour
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Herbal Medicines ◽  
The Body ◽  
Cutaneous Wound Healing ◽  
Skin Damage ◽  
Cutaneous Wound ◽  
Inflammatory Phase ◽  
Anti Inflammatory

Context: The skin is the most important organ of the body, and maintaining its integrity is important for health. Severe skin damage is life-threatening, and wound healing restores its integrity. One of the main health problems is impaired cutaneous wound healing. According to the importance of wound healing and the fact that unrepaired skin decreases the quality of life, many studies have investigated the effect of some natural and chemical substances on the length and quality of wound healing to find beneficial interventions for rapid and economical treatment. Objectives: This review was conducted to describe the physiology of cutaneous wound healing and some positive and negative factors affecting it with a focus on exercise. Methods: An electronic search without any time limitation was performed on the PubMed, Google Scholar, and Web of Science databases. The keywords were ‘wound’, ‘healing’, and ‘exercise’. Finally, according to the similarities or differences between the results and the relationship with the subject, 53 papers were selected and reviewed. Results: Wound healing is a complex physiological process with four overlapping processes. It seems that disturbance in the inflammatory phase of wound healing is the main factor in the impairment of healing. Traditionally, many chemical and herbal medicines and compounds have been used to speed up wound recovery due to their anti-inflammatory and antioxidative properties. Many studies have evaluated the effect of exercise, as complementary medicine, on wound healing, and they have examined the effect of different protocols of exercise on the speed of wound healing. According to the results of these studies, aerobic exercise, due to its anti-inflammatory and antioxidative effects, is a beneficial method in shortening the length of healing, especially in aged, obese, and diabetic individuals. Conclusions: Exercise as a low-cost intervention is a good strategy in the treatment of impaired and chronic wounds.

scholarly journals Prior Pro-inflammatory Polarization Changes the Macrophage Response to IL-4

2021 ◽  
Author(s):  
Erin M O'Brien ◽  
Kara L Spiller
Keyword(s):  
Tissue Repair ◽  
Chronic Wounds ◽  
Macrophage Polarization ◽  
Phenotypic Switching ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Macrophage Response ◽  
M1 Macrophage ◽  
Gene And Protein Expression ◽  
M2 Phenotype

Tissue repair is largely regulated by diverse macrophage populations whose functions are timing- and context-dependent. The early phase of healing is dominated by pro-inflammatory macrophages, also known as M1, followed by the emergence of a distinct and diverse population that is collectively referred to as M2. The extent of the diversity of the M2 population is unknown. M2 macrophages may originate directly from circulating monocytes or from phenotypic switching of pre-existing M1 macrophages within the site of injury. The differences between these groups have not been investigated, but have major implications for understanding and treating pathologies characterized by deficient M2 activation, such as chronic wounds, which also exhibit diminished M1 macrophage behavior. This study investigated the influence of prior M1 activation on human macrophage polarization to an M2 phenotype in response to IL-4 treatment in vitro. Compared to unactivated (M0) macrophages, M1 macrophages upregulated several receptors that promote the M2 phenotype, including the primary receptor for IL-4. M1 activation also changed the macrophage response to treatment with IL-4, generating an M2-like phenotype with a distinct gene and protein expression signature compared to M2 macrophages prepared directly from M0 macrophages. Functionally, compared to M0-derived M2 macrophages, M1-derived M2 macrophages demonstrated increased migratory response to SDF-1α, and conditioned media from these macrophages promoted increased recruitment of endothelial cells in transwell assays. Together, these findings indicate the importance of prior M1 activation in regulating subsequent M2 behavior, and suggest that augmentation of M1 behavior may be a therapeutic target in dysfunctional tissue repair.

scholarly journals Cervus nippon var. mantchuricus water extract treated with digestive enzymes (CE) modulates M1 macrophage polarization through TLR4/MAPK/NF-κB signaling pathways on murine macrophages

2021 ◽  
Vol 19 ◽  
pp. 205873922110008
Author(s):  
Se Hyang Hong ◽  
Jin Mo Ku ◽  
Ye Seul Lim ◽  
Hyo In Kim ◽  
Yong Cheol Shin ◽  
...  
Keyword(s):  
Digestive Enzymes ◽  
Macrophage Polarization ◽  
Water Extract ◽  
Cervus Nippon ◽  
No Production ◽  
M1 Macrophages ◽  
Murine Macrophages ◽  
M1 Macrophage ◽  
Tnf Α ◽  
Cytokine Levels

The objective of this study was to investigate the effects of Cervus nippon var. mantchuricus water extract treated with digestive enzymes (CE) on the promotion of M1 macrophage polarization in murine macrophages. Macrophages polarize either to one phenotype after stimulation with LPS or IFN-γ or to an alternatively activated phenotype that is induced by IL-4 or IL-13. Cell viability of RAW264.7 cells was determined by WST-1 assay. NO production was measured by Griess assay. IL-6, IL-12, TNF-α, and iNOS mRNA levels were measured by RT-PCR. IL-6, IL-12, and IL-10 cytokine levels were determined by ELISA. TLR4/MAPK/NF-κB signaling in RAW264.7 cells was evaluated by western blotting. The level of NF-κB was determined by immunoblotting. CE induced the differentiation of M1 macrophages. CE promoted M1 macrophages to elevate NO production and cytokine levels. CE-stimulated M1 macrophages had enhanced IL-6, IL-12, and TNF-α. CE promoted M1 macrophages to activate TLR4/MAPK/NF-κB phosphorylation. M2 markers were downregulated, while M1 markers were upregulated in murine macrophages by CE. Consequently, CE has immunomodulatory activity and can be used to promote M1 macrophage polarization through the TLR4/MAPK/NF-κB signaling pathways.

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.

Abstract 553: Siglec-1 (CD169) on Monocytes/Macrophages: A New Receptor For Extracellular Self-RNA in Triggering Inflammatory Responses via the Sheddase TACE/ADAM17

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Hector A Cabrera-Fuentes ◽  
Klaus T Preissner ◽  
William A Boisvert
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Transmembrane Protein ◽  
Macrophage Polarization ◽  
Extracellular Rna ◽  
Tnf Α ◽  
M1 Phenotype ◽  
Phenotype Markers ◽  
Anti Inflammatory

As an important component of atherosclerosis, monocytes/macrophages respond to external stimuli with rapid changes in their expression of many inflammation-related genes to undergo polarization towards the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotype. Although sialoadhesin (Sn), also known as SIGLEC-1 or CD169, is a transmembrane protein receptor expressed on monocytes and macrophages whether it has a role in macrophage polarization and ultimately, macrophage-driven atherogenesis, has not been investigated. We have previously shown that, independently of Toll-like receptor signaling, extracellular RNA (eRNA) could exert pro-thrombotic and pro-inflammatory properties in the cardiovascular system by inducing cytokine mobilization. In the current study, recombinant mouse macrophage CSF[[Unable to Display Character: –]]driven bone marrow-derived macrophage (BMDM) differentiation was found to be skewed towards the M1 phenotype by exposure of cells to eRNA. This resulted in up-regulation of inflammatory markers, whereas anti-inflammatory genes were significantly down-regulated by eRNA. Interestingly, eRNA was released from BMDM under hypoxia and induced TNF-α liberation by activating TNF-α converting enzyme (TACE) to provoke inflammation. Conversely, TNF-α promoted eRNA release, especially under hypoxia, feeding a vicious cycle of cell damage. Administration of RNase1 or TAPI (a TACE-inhibitor) prevented the production of inflammatory mediators. Murine BMDM isolated from mice deficient in sialoadhesin had the opposite reaction to eRNA treatment with a prominent down-regulation of pro-inflammatory cytokines/M1 phenotype markers, while anti-inflammatory cytokines/M2 phenotype markers were significantly raised. In keeping with the proposed role of eRNA as a pro-inflammatory “alarm signal”, these data further shed light on the role of eRNA in macrophage function in the context of chronic inflammatory diseases such as atherosclerosis. The identification of sialoadhesin as putative eRNA recognition site on macrophages may allow further investigation of the underlying mechanisms of eRNA-macrophage interaction and related signal transduction pathways. Siglec-1 thereby may provides a new target to treat eRNA-mediated vascular diseases.

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