scholarly journals Regulation of inflammatory signaling by the ST6Gal-I sialyltransferase

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241850
Author(s):  
Andrew T. Holdbrooks ◽  
Katherine E. Ankenbauer ◽  
Jihye Hwang ◽  
Susan L. Bellis
Keyword(s):  
Cell Model ◽  
Sialic Acids ◽  
Inflammatory Signaling ◽  
Monocytic Cell ◽  
Monocytic Cells ◽  
Gm Csf ◽  
Inflammatory Phenotype ◽  
U937 Monocytic Cell ◽  
St6gal I

The ST6Gal-I sialyltransferase, an enzyme that adds α2-6-linked sialic acids to N-glycosylated proteins, regulates multiple immunological processes. However, the contribution of receptor sialylation to inflammatory signaling has been under-investigated. In the current study, we uncovered a role for ST6Gal-I in promoting sustained signaling through two prominent inflammatory pathways, NFκB and JAK/STAT. Using the U937 monocytic cell model, we determined that knockdown (KD) of ST6Gal-I expression had no effect on the rapid activation of NFκB by TNF (≤ 30 min), whereas long-term TNF-induced NFκB activation (2–6 hr) was diminished in ST6Gal-I-KD cells. These data align with prior work in epithelial cells showing that α2–6 sialylation of TNFR1 prolongs TNF-dependent NFκB activation. Similar to TNF, long-term, but not short-term, LPS-induced activation of NFκB was suppressed by ST6Gal-I KD. ST6Gal-I KD cells also exhibited reduced long-term IRF3 and STAT3 activation by LPS. Given that ST6Gal-I activity modulated LPS-dependent signaling, we conducted pull-down assays using SNA (a lectin specific for α2–6 sialic acids) to show that the LPS receptor, TLR4, is a substrate for sialylation by ST6Gal-I. We next assessed signaling by IFNγ, IL-6 and GM-CSF, and found that ST6Gal-I-KD had a limited effect on STAT activation induced by these cytokines. To corroborate these findings, signaling was monitored in bone marrow derived macrophages (BMDMs) from mice with myeloid-specific deletion of ST6Gal-I (LysMCre/ST6Gal-Ifl/fl). In agreement with data from U937 cells, BMDMs with ST6Gal-I knockout displayed reduced long-term activation of NFκB by both TNF and LPS, and diminished long-term LPS-dependent STAT3 activation. However, STAT activation induced by IFNγ, IL-6 and GM-CSF was comparable in wild-type and ST6Gal-I knockout BMDMs. These results implicate ST6Gal-I-mediated receptor sialylation in prolonging the activity of select signaling cascades including TNF/NFκB, LPS/NFκB, and LPS/STAT3, providing new insights into ST6Gal-I’s role in modulating the inflammatory phenotype of monocytic cells.

A New Cellular Model for In Vitro Biocompatibility Evaluation of Microcapsule Materials

2005 ◽  
Vol 288-289 ◽  
pp. 499-502 ◽  
Author(s):  
Hua'an Zhang ◽  
Lin Sun ◽  
Wei Wang ◽  
Xiao Jun Ma
Keyword(s):  
Cell Model ◽  
L929 Cell ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Human Monocytic Cell Line ◽  
In Vitro Biocompatibility ◽  
Human Monocytic Cell ◽  
Biocompatibility Testing

Fibrosis caused by the host response to long-term transplanted microcapsules and the limitation of traditional L929 cell model for biocompatibility testing inspire the development of an assay of biocompatibility based on macrophage behavior. In this paper, the human monocytic cell line THP-1 was utilized for biocompatibility evaluation of microcapsule materials. The cell viability and secretion of nitric oxide (NO) and cytokines served as index of biocompatibility were assayed. It was found that the evaluated microcapsule materials had no effect on the stimulation of NO and cytokines secretion, which meant that these materials were biocompatible. Furthermore, it suggests the THP-1 cell a convenient in vitro experimental model that might be useful for long-term predictions of material biocompatibility.

IL-3, GM-CSF and CSF-1 modulate c-fms mRNA more rapidly in human early monocytic progenitors than in mature or transformed monocytic cells

1996 ◽  
Vol 109 (7) ◽  
pp. 1795-1801
Author(s):  
B. Panterne ◽  
A. Hatzfeld ◽  
P. Sansilvestri ◽  
A. Cardoso ◽  
M.N. Monier ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Activation ◽  
Bone Marrow Cells ◽  
Blood Monocytes ◽  
Monocytic Cell ◽  
Monocytic Cells ◽  
Gm Csf ◽  
Protein Levels ◽  
High Doses ◽  
Transformed Cell Lines

We have previously shown that a low concentration of CSF-1 (1 U/ml) can trigger human immature monocytic progenitor proliferation in the presence of low concentrations of IL3 (1.7 U/ml). No c-fms down-regulation was observed during this early cell activation. In contrast, 20 U/ml of CSF-1, active on late monocytic cell growth, down-regulated c-fms mRNA expression in immature progenitors and monocytes derived from bone marrow CD34+ cells in culture. We have now extended this study to include the effects of various concentrations of GM-CSF, IL3 and G-CSF on c-fms expression. We observed that high doses of GM-CSF or IL3 down-modulated c-fms mRNA, whereas low doses of GM-CSF or IL3, which were active on early monocytic growth, had no such effect. Similar results were observed at the protein level. In contrast, whatever the concentration, G-CSF had no effect on c-fms mRNA or protein levels. We further observed that the more immature the c-fms expressing progenitors, the faster the down-modulation of this receptor. This was observed within less than 1 hour for immature bone marrow cells, 6 hours for peripheral blood monocytes and even longer for transformed monocytic cells. These results suggest that oncogene expression can be regulated much more rapidly in immature progenitors than was previously observed in mature cells or transformed cell lines.

scholarly journals Mimicking of Blood Flow Results in a Distinct Functional Phenotype in Human Non-Adherent Classical Monocytes

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 748
Author(s):  
Elisa Wirthgen ◽  
Melanie Hornschuh ◽  
Ida Maria Wrobel ◽  
Christian Manteuffel ◽  
Jan Däbritz
Keyword(s):  
Blood Flow ◽  
Shear Flow ◽  
Ex Vivo ◽  
Culture Conditions ◽  
Inflammatory Signaling ◽  
Gm Csf ◽  
Beneficial Effects ◽  
Migratory Capacity ◽  
Ex Vivo Culture ◽  
Static Conditions

Ex vivo culture conditions during the manufacturing process impact the therapeutic effect of cell-based products. Mimicking blood flow during ex vivo culture of monocytes has beneficial effects by preserving their migratory ability. However, the effects of shear flow on the inflammatory response have not been studied so far. Hence, the present study investigates the effects of shear flow on both blood-derived naïve and activated monocytes. The activation of monocytes was experimentally induced by granulocyte-macrophage colony-stimulating factor (GM-CSF), which acts as a pro-survival and growth factor on monocytes with a potential role in inflammation. Monocytes were cultured under dynamic (=shear flow) or static conditions while preventing monocytes' adherence by using cell-repellent surfaces to avoid adhesion-induced differentiation. After cultivation (40 h), cell size, viability, and cytokine secretion were evaluated, and the cells were further applied to functional tests on their migratory capacity, adherence, and metabolic activity. Our results demonstrate that the application of shear flow resulted in a decreased pro-inflammatory signaling concurrent with increased secretion of the anti-inflammatory cytokine IL-10 and increased migratory capacity. These features may improve the efficacy of monocyte-based therapeutic products as both the unwanted inflammatory signaling in blood circulation and the loss of migratory ability will be prevented.

scholarly journals HIV induces airway basal progenitor cells to adopt an inflammatory phenotype

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nancy P. Y. Chung ◽  
K. M. Faisal Khan ◽  
Robert J. Kaner ◽  
Sarah L. O’Beirne ◽  
Ronald G. Crystal
Keyword(s):  
Progenitor Cells ◽  
Inflammatory Mediators ◽  
Lung Inflammation ◽  
Mapk Signaling ◽  
Gm Csf ◽  
Basal Progenitor ◽  
Inflammatory Phenotype ◽  
Mapk Signaling Pathways ◽  
Chronic Hiv Infection

AbstractDespite the introduction of anti-retroviral therapy, chronic HIV infection is associated with an increased incidence of other comorbidities such as COPD. Based on the knowledge that binding of HIV to human airway basal stem/progenitor cells (BC) induces a destructive phenotype by increased MMP-9 expression through MAPK signaling pathways, we hypothesized that HIV induces the BC to express inflammatory mediators that contribute to the pathogenesis of emphysema. Our data demonstrate that airway BC isolated from HAART-treated HIV+ nonsmokers spontaneously release inflammatory mediators IL-8, IL-1β, ICAM-1 and GM-CSF. Similarly, exposure of normal BC to HIV in vitro up-regulates expression of the same inflammatory mediators. These HIV-BC derived mediators induce migration of alveolar macrophages (AM) and neutrophils and stimulate AM proliferation. This HIV-induced inflammatory phenotype likely contributes to lung inflammation in HIV+ individuals and provides explanation for the increased incidence of COPD in HIV+ individuals.

Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3065-3075 ◽  
Author(s):  
Olena Klimchenko ◽  
Antonio Di Stefano ◽  
Birgit Geoerger ◽  
Sofiane Hamidi ◽  
Paule Opolon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Fetal Liver ◽  
Critical Role ◽  
Embryonic Stem ◽  
Blood Monocytes ◽  
Monocytic Cell ◽  
Monocytic Cells

Abstract The early emergence of macrophages and their large pattern of tissue distribution during development suggest that they may play a critical role in the initial steps of embryogenesis. In the present study, we show that monocytic cells derived from human embryonic stem cells (hESCs) and from fetal liver follow a differentiation pathway different to that of adult cells, leading to specific functions. Embryonic and fetal monocytic cells differentiated from a CD14lowCD16− precursor to form CD14highCD16+ cells without producing the CD14highCD16− cell population that predominates in adult peripheral blood. Both demonstrated an enhanced expression of genes encoding tissue-degrading enzymes, chemokines, and scavenger receptors, as was previously reported for M2 macrophages. Compared with adult blood monocytes, embryonic and fetal monocytic cells secreted high amounts of proteins acting on tissue remodeling and angiogenesis, and most of them expressed the Tie2 receptor. Furthermore, they promoted vascular remodeling in xenotransplanted human tumors. These findings suggest that the regulation of human fetal and embryonic monocytic cell differentiation leads to the generation of cells endowed mainly with anti-inflammatory and remodeling functions. Trophic and immunosuppressive functions of M2-polarized macrophages link fetus and tumor development, and hESCs offer a valuable experimental model for in vitro studies of mechanisms sustaining these processes.

Long term cultures of human monocytes in vitro impact of GM-CSF on survival and differentiation

1991 ◽  
Vol 143 (2) ◽  
pp. 209-221 ◽  
Author(s):  
A. Eischen ◽  
F. Vincent ◽  
J.P. Bergerat ◽  
B. Louis ◽  
A. Faradji ◽  
...  
Keyword(s):  
Human Monocytes ◽  
Gm Csf

scholarly journals Classification of Monocytes, Promonocytes and Monoblasts Using Deep Neural Network Models: An Area of Unmet Need in Diagnostic Hematopathology

2021 ◽  
Vol 10 (11) ◽  
pp. 2264
Author(s):  
Mazen Osman ◽  
Zeynettin Akkus ◽  
Dragan Jevremovic ◽  
Phuong L. Nguyen ◽  
Dana Roh ◽  
...  
Keyword(s):  
Unmet Need ◽  
Network Models ◽  
Ground Truth ◽  
Monocytic Differentiation ◽  
Neural Network Models ◽  
Monocytic Cell ◽  
Monocytic Cells ◽  
Blast Cells ◽  
Single Category ◽  
Improved Accuracy

The accurate diagnosis of chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) subtypes with monocytic differentiation relies on the proper identification and quantitation of blast cells and blast-equivalent cells, including promonocytes. This distinction can be quite challenging given the cytomorphologic and immunophenotypic similarities among the monocytic cell precursors. The aim of this study was to assess the performance of convolutional neural networks (CNN) in separating monocytes from their precursors (i.e., promonocytes and monoblasts). We collected digital images of 935 monocytic cells that were blindly reviewed by five experienced morphologists and assigned into three subtypes: monocyte, promonocyte, and blast. The consensus between reviewers was considered as a ground truth reference label for each cell. In order to assess the performance of CNN models, we divided our data into training (70%), validation (10%), and test (20%) datasets, as well as applied fivefold cross validation. The CNN models did not perform well for predicting three monocytic subtypes, but their performance was significantly improved for two subtypes (monocyte vs. promonocytes + blasts). Our findings (1) support the concept that morphologic distinction between monocytic cells of various differentiation level is difficult; (2) suggest that combining blasts and promonocytes into a single category is desirable for improved accuracy; and (3) show that CNN models can reach accuracy comparable to human reviewers (0.78 ± 0.10 vs. 0.86 ± 0.05). As far as we know, this is the first study to separate monocytes from their precursors using CNN.

scholarly journals Trans cohort metabolic reprogramming towards glutaminolysis in long-term successfully treated HIV-infection

2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Flora Mikaeloff ◽  
Sara Svensson Akusjärvi ◽  
George Mondinde Ikomey ◽  
Shuba Krishnan ◽  
Maike Sperk ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Cell Model ◽  
Antiretroviral Drugs ◽  
Metabolic Reprogramming ◽  
System Level ◽  
People Living With Hiv ◽  
Low Grade ◽  
Middle Income ◽  
Living With Hiv

AbstractDespite successful combination antiretroviral therapy (cART), persistent low-grade immune activation together with inflammation and toxic antiretroviral drugs can lead to long-lasting metabolic flexibility and adaptation in people living with HIV (PLWH). Our study investigated alterations in the plasma metabolic profiles by comparing PLWH on long-term cART(>5 years) and matched HIV-negative controls (HC) in two cohorts from low- and middle-income countries (LMIC), Cameroon, and India, respectively, to understand the system-level dysregulation in HIV-infection. Using untargeted and targeted LC-MS/MS-based metabolic profiling and applying advanced system biology methods, an altered amino acid metabolism, more specifically to glutaminolysis in PLWH than HC were reported. A significantly lower level of neurosteroids was observed in both cohorts and could potentiate neurological impairments in PLWH. Further, modulation of cellular glutaminolysis promoted increased cell death and latency reversal in pre-monocytic HIV-1 latent cell model U1, which may be essential for the clearance of the inducible reservoir in HIV-integrated cells.

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