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Arteriosclerosis, Thrombosis, and... Oct 2009
Topics: Cardiovascular Diseases; Humans; Monocytes
PubMed: 19759372
DOI: 10.1161/ATVBAHA.109.196048 -
The FEBS Journal Feb 2017Monocyte-to-macrophage differentiation is tightly controlled in vivo, as disruption of the normal differentiation program can lead to diverse disorders. Caspase-1, the...
Monocyte-to-macrophage differentiation is tightly controlled in vivo, as disruption of the normal differentiation program can lead to diverse disorders. Caspase-1, the first identified member of the caspase family, regulates differentiation in various cell types such as Th17 cells and adipocytes. However, the contribution of caspase-1 in monocyte-macrophage differentiation remains elusive. Here we report that caspase-1 is significantly downregulated in leukemia cells from patients with acute monocytic leukemia. By using the phorbol 12-myristate 13-acetate-induced cell differentiation model, we found that caspase-1 activation was required for the differentiation of human monocytes to macrophages. Further analysis of peroxisome proliferator-activated receptor γ (PPARγ) protein levels revealed that the monocyte-macrophage differentiation program could be divided into two stages. Caspase-1-mediated downregulation of PPARγ was important in the late stage of monocyte-macrophage differentiation; however, PPARγ protein levels had little effect on the early stage differentiation. Accumulation of PPARγ protein by troglitazone treatment potently suppressed the late stage of macrophage differentiation, which might be linked to inhibition of nuclear factor-κB activity. The data provide a plausible mechanistic basis by which caspase-1 promotes the differentiation of macrophages from monocytes.
Topics: Binding Sites; Caspase 1; Cell Differentiation; Chromans; Gene Expression Regulation; Humans; Hypoglycemic Agents; Leukemia, Monocytic, Acute; Macrophages; Monocytes; NF-kappa B; PPAR gamma; Primary Cell Culture; Protein Binding; Signal Transduction; Tetradecanoylphorbol Acetate; Thiazolidinediones; Troglitazone
PubMed: 28052562
DOI: 10.1111/febs.13998 -
Frontiers in Immunology 2023Lung transplantation often results in primary and/or chronic dysfunctions that are related to early perioperative innate allo-responses where myeloid subsets play a...
INTRODUCTION
Lung transplantation often results in primary and/or chronic dysfunctions that are related to early perioperative innate allo-responses where myeloid subsets play a major role. Corticosteroids are administered upon surgery as a standard-of-care but their action on the different myeloid cell subsets in that context is not known.
METHODS
To address this issue, we used a cross-circulatory platform perfusing an extracorporeal lung coupled to cell mapping in the pig model, that enabled us to study the recruited cells in the allogeneic lung over 10 hours.
RESULTS
Myeloid cells, i.e. granulocytes and monocytic cells including classical CD14 and non-classical/intermediate CD16 cells, were the dominantly recruited subsets, with the latter upregulating the membrane expression of MHC class II and CD80/86 molecules. Whereas corticosteroids did not reduce the different cell subset recruitment, they potently dampened the MHC class II and CD80/86 expression on monocytic cells and not on alveolar macrophages. Besides, corticosteroids induced a temporary and partial anti-inflammatory gene profile depending on cytokines and monocyte/macrophage subsets.
DISCUSSION
This work documents the baseline effects of the standard-of-care corticosteroid treatment for early innate allo-responses. These insights will enable further optimization and improvement of lung transplantation outcomes.
Topics: Animals; Swine; Monocytes; Myeloid Cells; Macrophages; Adrenal Cortex Hormones; Lung Transplantation
PubMed: 37942330
DOI: 10.3389/fimmu.2023.1281546 -
Psychiatry Research Aug 2012An inflammatory process is hypothesized in schizophrenia. Innate immunity, in particular the monocyte/macrophage system, has rarely been studied in this disorder,...
An inflammatory process is hypothesized in schizophrenia. Innate immunity, in particular the monocyte/macrophage system, has rarely been studied in this disorder, although alterations in microglia indicate a role for this system. Increased monocyte numbers have repeatedly been described. Toll-like receptors (TLRs) mediate the activation of monocytes. We studied the expression of the toll-like receptors TLR-2, TLR-3 and TLR-4 on CD14(+) monocytes in 31 schizophrenia patients and 31 sex- and age-matched healthy controls. Blood samples were taken and stimulated with either lipopolysaccharides (LPS), to mimic a bacterial infection, or polyI:C, to mimic a viral infection. Moreover, the intracellular concentration of interleukin-1ß (IL-1ß) in CD33(+) monocytes was estimated before and after stimulation. The intracellular concentrations of IL-1ß and the TLR surface markers were analyzed by flow cytometry. Receptor expression of TLR-3 and TLR-4, but not of TLR-2, was significantly higher in the schizophrenia patients. After stimulation, patients showed less increase in the expression of TLR-3 and TLR-4 than controls did. The IL-1ß concentration was significantly lower in patients both before and after stimulation with polyI:C, and there was a trend towards a lower concentration after LPS stimulation. The higher expression of TLR-3 and TLR-4 receptors might compensate for a functional deficit, and the lower intracellular concentrations of IL-1ß might reflect the blunted monocytic function in schizophrenia. The immunological dysfunctions might be associated with a poor clearance of pathogens in schizophrenia, which in turn could lead to a low-grade inflammatory process.
Topics: Adult; Case-Control Studies; Cell Proliferation; Female; Humans; Inflammation; Interleukin-1beta; Lipopolysaccharide Receptors; Lipopolysaccharides; Male; Monocytes; Poly I-C; Schizophrenia; Sialic Acid Binding Ig-like Lectin 3; Toll-Like Receptors
PubMed: 22429483
DOI: 10.1016/j.psychres.2011.12.049 -
Frontiers in Immunology 2021As hematopoietic progenitors supply a large number of blood cells, therapeutic strategies targeting hematopoietic progenitors are potentially beneficial to eliminate...
As hematopoietic progenitors supply a large number of blood cells, therapeutic strategies targeting hematopoietic progenitors are potentially beneficial to eliminate unwanted blood cells, such as leukemic cells and immune cells causing diseases. However, due to their pluripotency, targeting those cells may impair the production of multiple cell lineages, leading to serious side effects such as anemia and increased susceptibility to infection. To minimize those side effects, it is important to identify monopotent progenitors that give rise to a particular cell lineage. Monocytes and monocyte-derived macrophages play important roles in the development of inflammatory diseases and tumors. Recently, we identified human monocyte-restricted progenitors, namely, common monocyte progenitors and pre-monocytes, both of which express high levels of CD64, a well-known monocyte marker. Here, we introduce a dimeric pyrrolobenzodiazepine (dPBD)-conjugated anti-CD64 antibody (anti-CD64-dPBD) that selectively induces the apoptosis of proliferating human monocyte-restricted progenitors but not non-proliferating mature monocytes. Treatment with anti-CD64-dPBD did not affect other types of hematopoietic cells including hematopoietic stem and progenitor cells, neutrophils, lymphocytes and platelets, suggesting that its off-target effects are negligible. In line with these findings, treatment with anti-CD64-dPBD directly killed proliferating monocytic leukemia cells and prevented monocytic leukemia cell generation from bone marrow progenitors of chronic myelomonocytic leukemia patients in a patient-derived xenograft model. Furthermore, by depleting the source of monocytes, treatment with anti-CD64-dPBD ultimately eliminated tumor-associated macrophages and significantly reduced tumor size in humanized mice bearing solid tumors. Given the selective action of anti-CD64-dPBD on proliferating monocyte progenitors and monocytic leukemia cells, it should be a promising tool to target cancers and other monocyte-related inflammatory disorders with minimal side effects on other cell lineages.
Topics: Animals; Antineoplastic Agents, Immunological; Humans; Immunoconjugates; Immunophenotyping; Mice; Mice, Knockout; Mice, Transgenic; Monocyte-Macrophage Precursor Cells; Monocytes; THP-1 Cells; Tumor-Associated Macrophages
PubMed: 33692791
DOI: 10.3389/fimmu.2021.618081 -
Biochemical and Biophysical Research... Jan 2022Cholinergic anti-inflammatory pathway (CAP) describes a neuronal-inflammatory reflex centered on systemic cytokine regulation by α7 nicotinic acetylcholine receptor...
Cholinergic anti-inflammatory pathway (CAP) describes a neuronal-inflammatory reflex centered on systemic cytokine regulation by α7 nicotinic acetylcholine receptor (α7nAChR) activation of spleen-residue macrophage. However, the CAP mechanism attenuating distal tissue inflammation, inducing a low level of systemic inflammation, is lesser known. In this study, we hypothesized that CAP regulates monocyte accessibility by influencing their adhesion to endothelial cells. Using RNA-seq analysis, we identified that α1,3-Fucosyltransferase 7 (FucT-VII), the enzyme required for processing selectin ligands, was significantly downregulated by α7nAChR agonist among other cell-cell adhesion genes. The α7nAChR agonist inhibited monocytic cell line U-937 binding to P-selectin and adhesion to endothelial cells. Furthermore, α7nAChR agonist selectivity was confirmed by α7nAChR knockdown assays, showing that FUT7 inhibition and adhesion attenuation by the agonist was abolished by siRNA targeting α7nAChR encoding gene. Consistently, FUT7 knockdown inhibited the adhesive properties of U-937 and prevented them to adhere to endothelial cells. Overexpression of FUT7 also abrogated the adhesion attenuation induced by GTS-21 indicating that FUT7 inhibition was sufficient for inhibiting adhesion by α7nAChR activation. Our work demonstrated that α7nAChR activation regulates monocyte adhesion to endothelial cells through FUT7 inhibition, providing a novel insight into the CAP mechanism.
Topics: Benzylidene Compounds; Cell Adhesion; Down-Regulation; Fucosyltransferases; Gene Knockdown Techniques; Human Umbilical Vein Endothelial Cells; Humans; Monocytes; Pyridines; U937 Cells; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 34973535
DOI: 10.1016/j.bbrc.2021.12.094 -
Cell Reports Apr 2012Monocytes serve as a central defense system against infection and injury but can also promote pathological inflammatory responses. Considering the evidence that...
Monocytes serve as a central defense system against infection and injury but can also promote pathological inflammatory responses. Considering the evidence that monocytes exist in at least two subsets committed to divergent functions, we investigated whether distinct factors regulate the balance between monocyte subset responses in vivo. We identified a microRNA (miRNA), miR-146a, which is differentially regulated both in mouse (Ly-6C(hi)/Ly-6C(lo)) and human (CD14(hi)/CD14(lo)CD16(+)) monocyte subsets. The single miRNA controlled the amplitude of the Ly-6C(hi) monocyte response during inflammatory challenge whereas it did not affect Ly-6C(lo) cells. miR-146a-mediated regulation was cell-intrinsic and depended on Relb, a member of the noncanonical NF-κB/Rel family, which we identified as a direct miR-146a target. These observations not only provide mechanistic insights into the molecular events that regulate responses mediated by committed monocyte precursor populations but also identify targets for manipulating Ly-6C(hi) monocyte responses while sparing Ly-6Clo monocyte activity.
Topics: Animals; Cell Movement; Cell Proliferation; Gene Expression Regulation; Humans; Mice; MicroRNAs; Monocytes; Transcription Factor RelB
PubMed: 22545247
DOI: 10.1016/j.celrep.2012.02.009 -
Disease Markers 2010Our aim was to define the distribution of monocyte subsets in a cohort of congestive heart failure (CHF) patients, to verify whether increased severity of CHF is linked...
Our aim was to define the distribution of monocyte subsets in a cohort of congestive heart failure (CHF) patients, to verify whether increased severity of CHF is linked to the expansion of specific monocyte subsets, and finally to investigate the relationship between monocyte subset relative frequencies, laboratory parameters of inflammation, and monocyte ACE expression. Thirty consecutive CHF patients and 26 healthy control subjects were evaluated for peripheral blood monocyte expression of CD14, CD16 and CD143 (ACE) by flow-cytometry, and for endothelial-derived soluble CD146 levels by ELISA. CD14++ CD16+ frequency was significantly higher in CHF patients than in Controls (%, median value and IQ) (12.3, 8.7-14.8 vs 5.9, 4.7-6.9, p< 0.05, CHF vs Controls), and it increased depending on how high NYHA class was, on worsening LV ejection fraction and on circulating pro-BNP values. Furthermore, it was associated with increasing creatinine and with decreasing GFR and albumin levels. Monocyte CD143 expression was significantly elevated in CHF patients as compared to Controls, and positively associated with CD14++ CD16+ levels. Frequencies of CD14+ CD16+ monocytes were significantly lower in CHF patients as compared to Controls, and negatively correlated with levels of soluble CD146 (r=-0.529; p 0.048). In conclusion, monocytic CD14++ CD16+ frequency and CD143 levels are increased and reflect disease status and progressive cardiac deterioration in CHF patients. The CD14+ CD16+ subset is depleted in CHF and is linked to endothelial damage in this group of patients. Although the question of whether differences in monocyte CD14CD16 expansion are causal or whether they represent a marker of HF progression which is potentially relevant for risk prediction remains unanswered, we believe that our data represent an important tool for exploring the role of selective inflammatory pathways in CHF progression.
Topics: Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Cohort Studies; Disease Progression; GPI-Linked Proteins; Heart Failure; Humans; Inflammation Mediators; Kidney; Leukocyte Count; Lipopolysaccharide Receptors; Male; Monocytes; Neutrophils; Peptidyl-Dipeptidase A; Receptors, IgG
PubMed: 20364047
DOI: 10.3233/DMA-2010-0691 -
Nature Communications Aug 2017Little is known regarding the epigenetic basis of atherosclerosis. Here we present the CD14+ blood monocyte transcriptome and epigenome signatures associated with human...
Little is known regarding the epigenetic basis of atherosclerosis. Here we present the CD14+ blood monocyte transcriptome and epigenome signatures associated with human atherosclerosis. The transcriptome signature includes transcription coactivator, ARID5B, which is known to form a chromatin derepressor complex with a histone H3K9Me2-specific demethylase and promote adipogenesis and smooth muscle development. ARID5B CpG (cg25953130) methylation is inversely associated with both ARID5B expression and atherosclerosis, consistent with this CpG residing in an ARID5B enhancer region, based on chromatin capture and histone marks data. Mediation analysis supports assumptions that ARID5B expression mediates effects of cg25953130 methylation and several cardiovascular disease risk factors on atherosclerotic burden. In lipopolysaccharide-stimulated human THP1 monocytes, ARID5B knockdown reduced expression of genes involved in atherosclerosis-related inflammatory and lipid metabolism pathways, and inhibited cell migration and phagocytosis. These data suggest that ARID5B expression, possibly regulated by an epigenetically controlled enhancer, promotes atherosclerosis by dysregulating immunometabolism towards a chronic inflammatory phenotype.The molecular mechanisms mediating the impact of environmental factors in atherosclerosis are unclear. Here, the authors examine CD14+ blood monocyte's transcriptome and epigenome signatures to find differential methylation and expression of ARID5B to be associated with human atherosclerosis.
Topics: Aged; Atherosclerosis; DNA Methylation; DNA-Binding Proteins; Epigenesis, Genetic; Female; Histones; Humans; Male; Middle Aged; Monocytes; Transcription Factors; Transcriptome
PubMed: 28855511
DOI: 10.1038/s41467-017-00517-4 -
Acta Biochimica Et Biophysica Sinica Jul 2014Differentiation of monocytes into macrophages is an important process under physiological and pathological conditions, but the underlying mechanism of monocyte...
Differentiation of monocytes into macrophages is an important process under physiological and pathological conditions, but the underlying mechanism of monocyte differentiation is not completely clear. Some adhesion molecules have been reported to play an important role in cell differentiation. CD44 is an important adhesion molecule that mediates cell-cell and cell-matrix interaction, and participates in a wide variety of cellular functions. As CD44 has been reported to show different activated states between monocytes and macrophages, we propose that CD44 may be involved in monocyte differentiation. In this study, we explored the role of CD44 in monocyte differentiation and further studied the mechanisms that were involved in. THP-1 cells (human monocytic leukemia cell line) were induced with phorbol 12-myristate 13-acetate (PMA) to establish the model of monocyte differentiation in vitro. It was found that CD44 expression and binding capacity to hyaluronic acid were increased significantly, and the distribution of CD44 was converted into clusters during differentiation. The PMA-induced CD44 clustering and CD44 high expression were suppressed by blocking CD44, which resulted in the inhibition of CD14 expression. PMA-induced phosphorylation of ERK1/2 signal was also suppressed by blocking CD44. Our results suggested that CD44 was involved in monocyte differentiation. The mechanisms of monocyte differentiation following CD44 activation may include CD44 high expression and clustering which in turn lead to phosphorylation of ERK1/2.
Topics: Cell Differentiation; Cell Line, Tumor; Flow Cytometry; Humans; Hyaluronan Receptors; MAP Kinase Signaling System; Monocytes; Tetradecanoylphorbol Acetate
PubMed: 24850301
DOI: 10.1093/abbs/gmu042