Phenotypic activation and pharmacological outcomes of spontaneously differentiated human monocyte-derived macrophages

Tedesco, Serena; Bolego, Chiara; Toniolo, Alice; Nassi, Alberto; Fadini, Gian Paolo; Locati, Massimo; Cignarella, Andrea

doi:10.1016/j.imbio.2014.12.008

Cited by 80 publications

(76 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This designation, although conceptually useful, is an oversimplification of the phenotypic diversity of macrophages [55][56][57][58] . In reality, macrophages exhibit a complex progression of phenotypes that are affected by local signals as well as the stage of tissue remodeling [59][60][61] . Significant effort has been dedicated to modulate the phenotypic adaptation of macrophages as a therapeutic target for pathologies [62][63][64][65] .…”

mentioning

confidence: 99%

Nicotinamide Augments the Anti-Inflammatory Properties of Resveratrol through PARP1 Activation

Yanez

Jhanji

Murphy

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Resveratrol (RSV) and nicotinamide (NAM) have garnered considerable attention due to their anti-inflammatory and anti-aging properties. NAM is a transient inhibitor of class III histone deacetylase SIRTs (silent mating type information regulation 2 homologs) and SIRT1 is an inhibitor of poly-ADP-ribose polymerase-1 (PARP1). The debate on the relationship between RSV and SIRT1 has precluded the use of RSV as a therapeutic drug. Recent work demonstrated that RSV facilitates tyrosyl-tRNA synthetase (TyrRS)-dependent activation of PARP1. Moreover, treatment with NAM is sufficient to facilitate the nuclear localization of TyrRS that activates PARP1. RSV and NAM have emerged as potent agonists of PARP1 through inhibition of SIRT1. In this study, we evaluated the effects of RSV and NAM on pro-inflammatory macrophages. Our results demonstrate that treatment with either RSV or NAM attenuates the expression of pro-inflammatory markers. Strikingly, the combination of RSV with NAM, exerts additive effects on PARP1 activation. Consistently, treatment with PARP1 inhibitor antagonized the anti-inflammatory effect of both RSV and NAM. For the first time, we report the ability of NAM to augment PARP1 activation, induced by RSV, and its associated anti-inflammatory effects mediated through the induction of BCL6 with the concomitant down regulation of COX-2.

show abstract

mentioning

confidence: 99%

Nicotinamide Augments the Anti-Inflammatory Properties of Resveratrol through PARP1 Activation

Yanez

Jhanji

Murphy

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Obese individuals have increased numbers and proportions of peripheral blood monocytes [40], which led to the discovery that these blood findings were accompanied by increases of macrophages in the WAT compared with that of lean individuals. Furthermore, adipose tissue macrophages and peripheral blood monocytes in obese individuals are more likely to be polarized away from a M2 cell type and more toward a proinflammatory, or M1, cell type [34], a process that is driven, at least in part, by increased concentrations of IFN-γ and lipopolysaccharide [41]. M1 macrophages produce proinflammatory cytokines, including IL-6, TNF-α, and IL-1β [42].…”

Section: The Immune System As a Mediator Of Metabolic Syndromementioning

confidence: 99%

Metabolic Syndrome after Hematopoietic Cell Transplantation: At the Intersection of Treatment Toxicity and Immune Dysfunction

Turcotte

Yingst

Verneris

2016

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Hematopoietic cell transplantation (HCT) survivors face a multitude of short- and long-term health complications in the years after treatment. One important health complication that is associated with significant morbidity is metabolic syndrome (MetSyn). This constellation of findings, which includes obesity, glucose and lipid dysmetabolism, and hypertension, places affected individuals at increased risk for type 2 diabetes mellitus, cardiovascular complications, and stroke. Previous studies have linked MetSyn in HCT survivors to prior treatment; however, few studies have addressed the potential roles of systemic inflammation and immune system dysfunction after HCT. Within this review, we address the recent advances in the understanding of adipose tissue biology, immune, and inflammatory mechanisms involved in MetSyn in non-HCT patients, and lastly, we discuss potential novel mechanisms that may play a role in MetSyn development after HCT, such as hematopoietic stem cell source, inflammatory status of the stem cell donor, and microbiome composition, all of which represent potential new directions for post-HCT MetSyn research.

show abstract

“…Further, recent studies suggest a potential positive role of innate immunity in implant engraftment, whereby M2 macrophages are hypothesized to assist in healthy remodeling and vascularization. While dexamethasone is indicated to promote the M2 macrophage phenotype and a minimal impact on macrophage presence at the EFP site was observed, further studies are needed to clarify this role in vivo (71). Another potential impact of local dexamethasone delivery could be blood glucose dysregulation due to elevated systemic dexamethasone levels, which can lead to insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Controlled Release of Dexamethasone from Organosilicone Constructs for Local Modulation of Inflammation in Islet Transplantation

Weaver

Song

Yang

et al. 2015

Tissue Engineering Part A

View full text Add to dashboard Cite

Inflammation is a significant detriment to the engraftment of cells and tissues, particularly for islet transplantation, where a low tolerance for the inflammatory milieu results in significant graft loss. Local treatment with anti-inflammatories, such as glucocorticoids, provides the benefits of site-targeted delivery with minimization of the broad side effects associated with systemic delivery. Polydimethylsiloxane (PDMS) is a flexible platform that is capable of providing sustained delivery of hydrophobic drugs. Here, we evaluated the capacity of PDMS constructs loaded with the anti-inflammatory glucocorticoid dexamethasone (Dex) to locally mitigate inflammation in islet grafts. Dex-PDMS constructs, fabricated in rod or disk geometries, demonstrated prolonged and sustained release at therapeutically relevant levels. In vitro, Dex-PDMS constructs inhibited endotoxin-induced human monocyte and macrophage activation, but they did not impair islet viability or function. Dex-PDMS rods, co-transplanted with islet-seeded scaffolds in a murine model, demonstrated suppression of host inflammatory responses during early- and late-phase engraftment, without significantly altering islet graft potency. The facile nature of these glucocorticoid-doped PDMS constructs allows for the optimization of targeted dose delivery with wide applicability in cell and tissue transplantation.

show abstract

Phenotypic activation and pharmacological outcomes of spontaneously differentiated human monocyte-derived macrophages

Cited by 80 publications

References 41 publications

Nicotinamide Augments the Anti-Inflammatory Properties of Resveratrol through PARP1 Activation

Nicotinamide Augments the Anti-Inflammatory Properties of Resveratrol through PARP1 Activation

Metabolic Syndrome after Hematopoietic Cell Transplantation: At the Intersection of Treatment Toxicity and Immune Dysfunction

Controlled Release of Dexamethasone from Organosilicone Constructs for Local Modulation of Inflammation in Islet Transplantation

Contact Info

Product

Resources

About