Effect of M2 Macrophage-Derived Soluble Factors on Behavioral Patterns and Cytokine Production in Various Brain Structures in Depression-Like Mice

2022 ◽  
Author(s):  
E. V. Markova ◽  
E. Ya. Shevela ◽  
M. A. Knyazeva ◽  
I. V. Savkin ◽  
E. V. Serenko ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Brain Structures ◽  
M2 Macrophage ◽  
Behavioral Patterns ◽  
Soluble Factors

scholarly journals Inflammatory Mediators and Insulin Resistance in Obesity: Role of Nuclear Receptor Signaling in Macrophages

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Lucía Fuentes ◽  
Tamás Rőszer ◽  
Mercedes Ricote
Keyword(s):  
Insulin Resistance ◽  
Nuclear Receptor ◽  
Cytokine Production ◽  
Current Knowledge ◽  
Liver Steatosis ◽  
Visceral Obesity ◽  
M2 Macrophage ◽  
Low Grade ◽  
The Impact

Visceral obesity is coupled to a general low-grade chronic inflammatory state characterized by macrophage activation and inflammatory cytokine production, leading to insulin resistance (IR). The balance between proinflammatory M1 and antiinflammatory M2 macrophage phenotypes within visceral adipose tissue appears to be crucially involved in the development of obesity-associated IR and consequent metabolic abnormalities. The ligand-dependent transcription factors peroxisome proliferator activated receptors (PPARs) have recently been implicated in the determination of the M1/M2 phenotype. Liver X receptors (LXRs), which form another subgroup of the nuclear receptor superfamily, are also important regulators of proinflammatory cytokine production in macrophages. Disregulation of macrophage-mediated inflammation by PPARs and LXRs therefore underlies the development of IR. This review summarizes the role of PPAR and LXR signaling in macrophages and current knowledge about the impact of these actions in the manifestation of IR and obesity comorbidities such as liver steatosis and diabetic osteopenia.

Effect of M2 Macrophage-Derived Soluble Factors on Proliferation and Apoptosis of SH-SY5Y Cells

2021 ◽  
Author(s):  
I. M. Rashchupkin ◽  
A. A. Maksimova ◽  
L. V. Sakhno ◽  
A. A. Ostanin ◽  
E. Ya. Shevela ◽  
...  
Keyword(s):  
M2 Macrophage ◽  
Soluble Factors ◽  
Proliferation And Apoptosis

scholarly journals EFFECT OF M2 MACROPHAGE-DERIVED SOLUBLE FACTORS ON DIFFERENTIATION OF SH-SY5Y CELLS

2021 ◽  
Vol 23 (4) ◽  
pp. 677-684
Author(s):  
I. M. Rashchupkin ◽  
E. Ya. Shevela ◽  
E. R. Chernykh
Keyword(s):  
Retinoic Acid ◽  
Conditioned Medium ◽  
Neuronal Differentiation ◽  
Macrophage Polarization ◽  
Relative Content ◽  
M2 Macrophage ◽  
Neurite Length ◽  
Soluble Factors ◽  
Differentiated Cells ◽  
Morphological Criteria

Macrophages play a key role in triggering and regulation of neuroregeneration. The characteristic feature of macrophages is pronounced plasticity, which manifests itself in the ability of macrophages to change their functional phenotype depending on the micromilieu. Apoptotic cell clearance (efferocytosis) is an important inducer of a macrophage polarization to M2 phenotype under pathological settings. Previously, we have developed an original protocol for the generation of M2-like macrophages, polarized by efferocytosis under serum-deprived conditions (M2 (LS), Low Serum). The present study was aimed to assess a neuroregenerative potential of M2 (LS) macrophages. We studied their effect on the differentiation of SH-SY5Y cells in comparison with retinoic acid (RA). As the morphological criteria of differentiation we have assessed the relative content of differentiated cells, i.e., cells with a neurite length exceeding the cell body length, and the average neurite length on days 3, 7, and 13. The ratio of neuron-like (N-type) and epithelial-like (S-type) cells in cultures was also assessed. SH-SY5Y cells were characterized by a low level of spontaneous differentiation, both under standard conditions (10% FBS) and serum deprivation (1% FBS). Upon RA treatment, SH-SY5Y cells stopped proliferating and underwent neuronal differentiation. Cultivation of SH-SY5Y cells in the presence of M2 (LS) conditioned medium also led to a significant increase in the relative content of differentiated cells, the average length of neurite-like processes, as well as a change in the balance of S- and N-type cells towards a pronounced predominance of the latter. The morphological features of differentiation were significantly less pronounced at early stage (day 3) of differentiation as compared with the RA-induced changes and reached the level of positive control only at later stages (day 13) (p < 0.05). In contrast to retinoic acid, M2 (LS) conditioned medium induced neuronal differentiation of SH-SY5Y cells without suppressing their proliferative activity. The data obtained may indicate a high neuroregenerative potential of M2 macrophages in vitro, which is realized through soluble factors and manifests itself in promoting SH-SY5Y differentiation. 

The effect of M2 macrophage-derived soluble factors on proliferation and apoptosis of SH-SY5Y cells

2021 ◽  
Vol 171 (1) ◽  
pp. 59-63
Author(s):  
I. M. Rashchupkin ◽  
◽  
A. A. Maksimova ◽  
L. V. Sakhno ◽  
A. A. Ostanin ◽  
...  
Keyword(s):  
M2 Macrophage ◽  
Soluble Factors ◽  
Proliferation And Apoptosis

scholarly journals Orexin A content in brain structures correlates with behavioral patterns in stressed rats

2018 ◽  
Vol 16 (4) ◽  
pp. 45-48
Author(s):  
Platon P. Khokhlov ◽  
Ilia Yu. Tissen ◽  
Andrei A. Lebedev ◽  
Eugenii R. Bychkov ◽  
Petr D. Shabanov
Keyword(s):  
Open Field ◽  
Elevated Plus Maze ◽  
Rank Correlation ◽  
Brain Structures ◽  
Emotional Behavior ◽  
Behavioral Patterns ◽  
Orexin A ◽  
Spearman’S Rank Correlation ◽  
Plus Maze ◽  
The Brain

The aim of this investigation was to reveal correlations between some behavioral patterns and orexin concentrations in the brain structures in rats after an acute psychoemotional stress. A group of rats was placed into a chamber with a tiger python for 25 mi nutes and then as a treatment these rats received orexin A or its antagonist SB-408124 administered intranasally for 7 days. Then the quantitive indexes of behavioral patterns in open field and elevated plus maze were registered. The orexin A level was investigated in the brain structures (amygdala, hippocampus, hypothalamus) of such rats by means of high-sensitive ELISA. The correlations were assessed with Spearman’s rank correlation test. As a result, a correlation between orexin A content in the amygdala and hypothalamus and a number of ambulations (line crossings) characterizing motor activity in open field test has been revealed. Therefore, the level of orexin A in the amygdala and hypothalamus demonstrates a direct and reverse link with locomotor activity of rats respectively. Also a correlation between orexin A level in the hippocampus and amygdala and the time of staying in the dark alleys of the elevated plus maze has been revealed. So, the content of orexin A in the hippocampus and amygdala reflects anxiety level of a rat. It is concluded there is a positive correlation between the orexin A content in the limbic structures of the brain and emotional behavior of rats.

scholarly journals The differential statin effect on cytokine production of monocytes or macrophages is mediated by differential geranylgeranylation-dependent Rac1 activation

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Hang Fu ◽  
Mohamad Alabdullah ◽  
Julia Großmann ◽  
Florian Spieler ◽  
Reem Abdosh ◽  
...  
Keyword(s):  
Cholesterol Synthesis ◽  
Cytokine Production ◽  
Inflammatory Diseases ◽  
Mevalonic Acid ◽  
M2 Macrophage ◽  
Cd163 Expression ◽  
Monocytes And Macrophages ◽  
Factor Α ◽  
Functional Capacities ◽  
Interfering Rna

AbstractMonocytes and macrophages contribute to pathogenesis of various inflammatory diseases, including auto-inflammatory diseases, cancer, sepsis, or atherosclerosis. They do so by production of cytokines, the central regulators of inflammation. Isoprenylation of small G-proteins is involved in regulation of production of some cytokines. Statins possibly affect isoprenylation-dependent cytokine production of monocytes and macrophages differentially. Thus, we compared statin-dependent cytokine production of lipopolysaccharide (LPS)-stimulated freshly isolated human monocytes and macrophages derived from monocytes by overnight differentiation. Stimulated monocytes readily produced tumor necrosis factor-α, interleukin-6, and interleukin-1β. Statins did not alter cytokine production of LPS-stimulated monocytes. In contrast, monocyte-derived macrophages prepared in the absence of statin lost the capacity to produce cytokines, whereas macrophages prepared in the presence of statin still produced cytokines. The cells expressed indistinguishable nuclear factor-kB activity, suggesting involvement of separate, statin-dependent regulation pathways. The presence of statin was necessary during the differentiation phase of the macrophages, indicating that retainment-of-function rather than costimulation was involved. Reconstitution with mevalonic acid, farnesyl pyrophosphate, or geranylgeranyl pyrophosphate blocked the retainment effect, whereas reconstitution of cholesterol synthesis by squalene did not. Inhibition of geranylgeranylation by GGTI-298, but not inhibition of farnesylation or cholesterol synthesis, mimicked the retainment effect of the statin. Inhibition of Rac1 activation by the Rac1/TIAM1-inhibitor NSC23766 or by Rac1-siRNA (small interfering RNA) blocked the retainment effect. Consistent with this finding, macrophages differentiated in the presence of statin expressed enhanced Rac1-GTP-levels. In line with the above hypothesis that monocytes and macrophages are differentially regulated by statins, the CD14/CD16-, merTK-, CX3CR1-, or CD163-expression (M2-macrophage-related) correlated inversely to the cytokine production. Thus, monocytes and macrophages display differential Rac1-geranylgeranylation-dependent functional capacities, that is, statins sway monocytes and macrophages differentially.

scholarly journals Characterization of Cytotoxic Macrophages in a Pre-Clinical Model of Epstein-Barr Virus (EBV)-Driven Lymphoproliferative Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3502-3502
Author(s):  
John Patton ◽  
Emily Smith ◽  
Zahary Smith ◽  
Andrew Stiff ◽  
A. Douglas Kinghorn ◽  
...  
Keyword(s):  
T Cells ◽  
Epstein Barr Virus ◽  
Tumor Response ◽  
Myeloid Cells ◽  
M2 Macrophage ◽  
Soluble Factors ◽  
Clinical Model ◽  
Barr Virus ◽  
Epstein Barr ◽  
Autologous Cd14

Abstract Epstein-Barr Virus (EBV) is an oncogenic herpes virus associated with the development of malignancies associated with poor outcomes. Current treatments lead to further immune suppression, increasing the risk of EBV reactivation and other opportunistic infections. Strategies aimed at reversing the immune-suppressive microenvironment are likely to result in more durable responses while avoiding deleterious effects of chemotherapy. It is well-established that macrophages play an important role in inhibiting the anti-tumor response as evidenced by poor prognosis associated with increasing tumor-associated macrophage (TAM) density or lower ratio of cytotoxic T lymphocytes. Here we describe a pre-clinical model showing the expansion of cytotoxic TAMs and potential mechanisms to prevent this immunosuppressive environment. To assess soluble factors produced by the interaction of tumor on immune effector cells, we used a co-culture (CoCx) system of EBV-transformed human B cell lymphoblastoid cell lines (LCL) cultured with autologous peripheral blood mononuclear cells (PBMC). Serum-free medium collected after 48 hrs showed increased myeloid-associated factors which were absent from either the LCL or PBMC cultures, suggesting the interaction of tumor cells with immune effectors was leading to the production of chemokines known to attract myeloid cells. When purified autologous CD14+ monocytes were incubated in the presence of CoCx conditioned medium (CM) they generated proliferative foci that were absent in the LCL or PBMC CM alone. To better understand which cellular subsets were necessary for the release of these soluble factors, immune subsets were removed from PBMC prior to incubation with LCL or purified and incubated with LCL. We found that T cells, (CD8+ and CD4+), when incubated in the presence of LCL were necessary and sufficient to stimulate the proliferation of myeloid cells. CD56+, CD14+, or CD19+ subsets within the CM did not appear to contribute to the proliferation of purified myeloid cells. We next used flow cytometry to characterize the monocyte-derived population that expanded when introduced to CoCx CM. We again isolated autologous CD14+ monocytes from PMBC and incubated them for 6 days with CoCx CM followed by immunophenotyping. The monocyte-derived population retained CD14 and CD11b in addition to showing pronounced increases in both canonical M1 and M2 macrophage markers (HLA-DR, and CD163 respectively), and PD-L1, indicating activation consistent with a TAM phenotype. To characterize the functional consequence of this cell population, CoCx CM-derived macrophages were incubated with autologous T cells that were either activated non-specifically with anti-CD3/C28 or left inactivated. Surprisingly, we noted a marked decrease in viable activated T cells (both CD4+ and CD8+) when exposed to conditioned macrophages. However, the inactivated T cell populations were only mildly effected. Together, with previously described experiments, this suggests a mechanism by which exposure of T cells to EBV+ lymphoblastic tumor lines results in cytokine release, polarizing monocytes to TAMs that, in turn, exhibit cytotoxic activity to tumor-specific T cells. The precise mechanism of cytotoxicity is under investigation. We previously reported the eIF4A translational inhibitor silvestrol potentiated a potent immune-mediated anti-tumor response against EBV-driven lymphoma mainly by promoting expansion and activity of EBV-specific cytotoxic T cells. We next questioned if macrophages were important to this mechanism. We found that with silvestrol, when added to CoCx, the resultant CM did not drive the proliferation of TAMs, and Immunophenotype of CoCx showed silvestrol treatment to result in the ablation of CD14+ cells from culture. Interrogation by transcriptome analysis indicated a potential role of aryl hydrocarbon receptor (AhR). Protein analysis by western blotting indicated an increase of AhR in isolated monocytes when exposed to CoCx CM, which was abrogated by addition of silvestrol. Together these results suggest AhR may play a role in the polarization of macrophages within the tumor microenvironment leading to elimination of tumor-specific T cells. While full mechanistic characterization is ongoing, these preliminary results provide a potentially novel approach to modulate tumor specific immunity in this challenging group of EBV-related malignancies. Disclosures Baiocchi: Prelude Therapeutics: Consultancy; viracta: Consultancy, Current holder of stock options in a privately-held company; Codiak Biosciences: Research Funding; Atara Biotherapeutics: Consultancy.

scholarly journals Cervical Cancer Cell Supernatants Induce a Phenotypic Switch from U937-Derived Macrophage-Activated M1 State into M2-Like Suppressor Phenotype with Change in Toll-Like Receptor Profile

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Karina Sánchez-Reyes ◽  
Alejandro Bravo-Cuellar ◽  
Georgina Hernández-Flores ◽  
José Manuel Lerma-Díaz ◽  
Luis Felipe Jave-Suárez ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Toll Like Receptor ◽  
Soluble Factors ◽  
Immune Effector ◽  
Effector Cells ◽  
M1 Macrophage ◽  
Receptor Profile ◽  
Alternatively Activated

Cervical cancer (CC) is the second most common cancer among women worldwide. Infection with human papillomavirus (HPV) is the main risk factor for developing CC. Macrophages are important immune effector cells; they can be differentiated into two phenotypes, identified as M1 (classically activated) and M2 (alternatively activated). Macrophage polarization exerts profound effects on the Toll-like receptor (TLR) profile. In this study, we evaluated whether the supernatant of human CC cells HeLa, SiHa, and C-33A induces a shift of M1 macrophage toward M2 macrophage in U937-derived macrophages.Results. The results showed that soluble factors secreted by CC cells induce a change in the immunophenotype of macrophages from macrophage M1 into macrophage M2. U937-derived macrophages M1 released proinflammatory cytokines and nitric oxide; however, when these cells were treated with the supernatant of CC cell lines, we observed a turnover of M1 toward M2. These cells increased CD163 and IL-10 expression. The expression of TLR-3, -7, and -9 is increased when the macrophages were treated with the supernatant of CC cells.Conclusions. Our result strongly suggests that CC cells may, through the secretion of soluble factors, induce a change of immunophenotype M1 into M2 macrophages.

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