Primary human monocytes differentiate into M2 macrophages and involve Notch-1 pathway

Singla, Dinender K.; Wang, Jing; Singla, Reetu D.

doi:10.1139/cjpp-2016-0319

Cited by 31 publications

(23 citation statements)

References 21 publications

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“…Defects in NF-κB p50 nuclear localization were observed in DAPT-treated macrophages and in RBP-Jκ-deficent macrophages, indicative of crosstalk between Notch and NF-κB pathways [275]. Lastly, DAPT treatment during MI diminished the number of macrophages in the infarcted area and significantly increased the M2 macrophage polarization [276], data resembling those obtained by Singla et al that confirmed reduction of the proinflammatory M1 phenotype following monocyte treatment with DAPT or Notch-1 siRNA [277].…”

Section: Notch In Macrophagessupporting

confidence: 77%

The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway

Aquila

Marracino

Martino

et al. 2019

Oxidative Medicine and Cellular Longevity

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Despite the currently available pharmacotherapies, today, thirty percent of worldwide deaths are due to cardiovascular diseases (CVDs), whose primary cause is atherosclerosis, an inflammatory disorder characterized by the buildup of lipid deposits on the inside of arteries. Multiple cellular signaling pathways have been shown to be involved in the processes underlying atherosclerosis, and evidence has been accumulating for the crucial role of Notch receptors in regulating the functions of the diverse cell types involved in atherosclerosis onset and progression. Several classes of nutraceuticals have potential benefits for the prevention and treatment of atherosclerosis and CVDs, some of which could in part be due to their ability to modulate the Notch pathway. In this review, we summarize the current state of knowledge on the role of Notch in vascular health and its modulation by nutraceuticals for the prevention of atherosclerosis and/or treatment of related CVDs.

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Section: Notch In Macrophagessupporting

confidence: 77%

The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway

Aquila

Marracino

Martino

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…The regulation and function of Notch signaling in myeloid cells involved in innate immunity is poorly understood. Nevertheless, recent findings elucidate a role for the Notch pathway during TLR-associated and inflammation-induced monocyte differentiation and macrophage activation (Radtke et al, 2010 ; Nakano et al, 2016 ; Singla et al, 2017 ). Cells of the myeloid lineage do express a broad range of TLRs as well as Notch receptors and ligands.…”

Section: Discussionmentioning

confidence: 99%

The Interplay of Notch Signaling and STAT3 in TLR-Activated Human Primary Monocytes

Hildebrand

Uhle

Sahin

et al. 2018

Front. Cell. Infect. Microbiol.

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The highly conserved Notch signaling pathway essentially participates in immunity through regulation of developmental processes and immune cell activity. In the adaptive immune system, the impact of the Notch cascade in T and B differentiation is well studied. In contrast, the function, and regulation of Notch signaling in the myeloid lineage during infection is poorly understood. Here we show that TLR signaling, triggered through LPS stimulation or in vitro infection with various Gram-negative and -positive bacteria, stimulates Notch receptor ligand Delta-like 1 (DLL1) expression and Notch signaling in human blood-derived monocytes. TLR activation induces DLL1 indirectly, through stimulated cytokine expression and autocrine cytokine receptor-mediated signal transducer and activator of transcription 3 (STAT3). Furthermore, we reveal a positive feedback loop between Notch signaling and Janus kinase (JAK)/STAT3 pathway during in vitro infection that involves Notch-boosted IL-6. Inhibition of Notch signaling by γ-secretase inhibitor DAPT impairs TLR4-stimulated accumulation of NF-κB subunits p65 in the nucleus and subsequently reduces LPS- and infection-mediated IL-6 production. The reduced IL-6 release correlates with a diminished STAT3 phosphorylation and reduced expression of STAT3-dependent target gene programmed death-ligand 1 (PD-L1). Corroborating recombinant soluble DLL1 and Notch activator oxaliplatin stimulate STAT3 phosphorylation and expression of immune-suppressive PD-L1. Therefore we propose a bidirectional interaction between Notch signaling and STAT3 that stabilizes activation of the transcription factor and supports STAT3-dependent remodeling of myeloid cells toward an immuno-suppressive phenotype. In summary, the study provides new insights into the complex network of Notch regulation in myeloid cells during in vitro infection. Moreover, it points to a participation of Notch in stabilizing TLR-mediated STAT3 activation and STAT3-mediated modulation of myeloid functional phenotype through induction of immune-suppressive PD-L1.

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“…These macrophages exhibited strong antitumor activities in transplanted tumors ( 19 ). Conversely, Notch blockade by GSI, small interfering RNA, or RBP-Jk deletion switches macrophages to M2 phenotype, characterized by the ability to produce IL-10 and an attenuated capacity of activating Th1 cells ( 20 , 21 ). Consistently, T cells activated by RBP-Jk−/− macrophage showed a reduced cytotoxic activity against melanoma cells when compared with wild-type macrophages ( 20 ).…”

Section: Interleukin 10mentioning

confidence: 99%

Cancer Cells Exploit Notch Signaling to Redefine a Supportive Cytokine Milieu

Colombo

Mirandola²,

Chiriva‐Internati

et al. 2018

Front. Immunol.

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Notch signaling is a well-known key player in the communication between adjacent cells during organ development, when it controls several processes involved in cell differentiation. Notch-mediated communication may occur through the interaction of Notch receptors with ligands on adjacent cells or by a paracrine/endocrine fashion, through soluble molecules that can mediate the communication between cells at distant sites. Dysregulation of Notch pathway causes a number of disorders, including cancer. Notch hyperactivation may be caused by mutations of Notch-related genes, dysregulated upstream pathways, or microenvironment signals. Cancer cells may exploit this aberrant signaling to “educate” the surrounding microenvironment cells toward a pro-tumoral behavior. This may occur because of key cytokines secreted by tumor cells or it may involve the microenvironment through the activation of Notch signaling in stromal cells, an event mediated by a direct cell-to-cell contact and resulting in the increased secretion of several pro-tumorigenic cytokines. Up to now, review articles were mainly focused on Notch contribution in a specific tumor context or immune cell populations. Here, we provide a comprehensive overview on the outcomes of Notch-mediated pathological interactions in different tumor settings and on the molecular and cellular mediators involved in this process. We describe how Notch dysregulation in cancer may alter the cytokine network and its outcomes on tumor progression and antitumor immune response.

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Primary human monocytes differentiate into M2 macrophages and involve Notch-1 pathway

Cited by 31 publications

References 21 publications

The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway

The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway

The Interplay of Notch Signaling and STAT3 in TLR-Activated Human Primary Monocytes

Cancer Cells Exploit Notch Signaling to Redefine a Supportive Cytokine Milieu

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