Real‐time imaging of inflammation and its resolution: It’s apparent because it’s transparent*

Robertson, Tanner F.; Huttenlocher, Anna

doi:10.1111/imr.13061

Cited by 15 publications

(13 citation statements)

References 175 publications

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“…Zebrafish represents a very useful in vivo experimental model to study changes in the inflammation milieu [ 25 ]. To generate a systemic delivery, EVs were microinjected into the duct of Cuvier of 48 hpf embryos.…”

Section: Resultsmentioning

confidence: 99%

PCSK9 Confers Inflammatory Properties to Extracellular Vesicles Released by Vascular Smooth Muscle Cells

Greco

Rizzuto

Zara

et al. 2022

IJMS

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Vascular smooth muscle cells (VSMCs) are key participants in both early- and late-stage atherosclerosis and influence neighbouring cells possibly by means of bioactive molecules, some of which are packed into extracellular vesicles (EVs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is expressed and secreted by VSMCs. This study aimed to unravel the role of PCSK9 on VSMCs-derived EVs in terms of content and functionality. EVs were isolated from human VSMCs overexpressing human PCSK9 (VSMCPCSK9-EVs) and tested on endothelial cells, monocytes, macrophages and in a model of zebrafish embryos. Compared to EVs released from wild-type VSMCs, VSMCPCSK9-EVs caused a rise in the expression of adhesion molecules in endothelial cells and of pro-inflammatory cytokines in monocytes. These acquired an increased migratory capacity, a reduced oxidative phosphorylation and secreted proteins involved in immune response and immune effector processes. Concerning macrophages, VSMCPCSK9-EVs enhanced inflammatory milieu and uptake of oxidized low-density lipoproteins, whereas the migratory capacity was reduced. When injected into zebrafish embryos, VSMCPCSK9-EVs favoured the recruitment of macrophages toward the site of injection. The results of the present study provide evidence that PCSK9 plays an inflammatory role by means of EVs, at least by those derived from smooth muscle cells of vascular origin.

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Section: Resultsmentioning

confidence: 99%

PCSK9 Confers Inflammatory Properties to Extracellular Vesicles Released by Vascular Smooth Muscle Cells

Greco

Rizzuto

Zara

et al. 2022

IJMS

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“…Given the fact that SM and its derivatives not only show high antitumor but also promising anti-inflammatory effects proven on various inflammatory murine models [ 16 , 18 , 19 , 20 , 54 ], we next questioned whether the formation of epoxide moiety in the pharmacophore group of SM affects the anti-inflammatory potential of the triterpenoid. To explore this, the effects of αO-SM and βO-SM on (i) the ability of murine J774 macrophages to produce nitric oxide (II) (NO), a known pro-inflammatory mediator [ 55 ], and (ii) the migration capacity of macrophages, playing an important role in the inflammatory process [ 56 ], were evaluated.…”

Section: Resultsmentioning

confidence: 99%

Novel Epoxides of Soloxolone Methyl: An Effect of the Formation of Oxirane Ring and Stereoisomerism on Cytotoxic Profile, Anti-Metastatic and Anti-Inflammatory Activities In Vitro and In Vivo

Salomatina

Sen’kova

Moralev

et al. 2022

IJMS

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It is known that epoxide-bearing compounds display pronounced pharmacological activities, and the epoxidation of natural metabolites can be a promising strategy to improve their bioactivity. Here, we report the design, synthesis and evaluation of biological properties of αO-SM and βO-SM, novel epoxides of soloxolone methyl (SM), a cyanoenone-bearing derivative of 18βH-glycyrrhetinic acid. We demonstrated that the replacement of a double-bound within the cyanoenone pharmacophore group of SM with α- and β-epoxide moieties did not abrogate the high antitumor and anti-inflammatory potentials of the triterpenoid. It was found that novel SM epoxides induced the death of tumor cells at low micromolar concentrations (IC50(24h) = 0.7–4.1 µM) via the induction of mitochondrial-mediated apoptosis, reinforced intracellular accumulation of doxorubicin in B16 melanoma cells, probably by direct interaction with key drug efflux pumps (P-glycoprotein, MRP1, MXR1), and the suppressed pro-metastatic phenotype of B16 cells, effectively inhibiting their metastasis in a murine model. Moreover, αO-SM and βO-SM hampered macrophage functionality in vitro (motility, NO production) and significantly suppressed carrageenan-induced peritonitis in vivo. Furthermore, the effect of the stereoisomerism of SM epoxides on the mentioned bioactivities and toxic profiles of these compounds in vivo were evaluated. Considering the comparable antitumor and anti-inflammatory effects of SM epoxides with SM and reference drugs (dacarbazine, dexamethasone), αO-SM and βO-SM can be considered novel promising antitumor and anti-inflammatory drug candidates.

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“…Studies in transparent zebrafish have previously uncovered new mechanisms of immune cell migration and behavior in situ (10)(11)(12)(13), and this model organism provides a unique opportunity to investigate T cell surveillance in an organism lacking lymph nodes. Utilizing a combination of microscopy and single cell RNA-sequencing (scRNA-seq), we first identified a novel whole-body lymphoid tissue that encompasses the major cellular hallmarks of a mammalian lymph node.…”

Section: Introductionmentioning

confidence: 99%

A tessellated lymphoid network provides whole-body T cell surveillance in zebrafish

Robertson

Hou

Shen

et al. 2023

Preprint

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Homeostatic trafficking to lymph nodes allows T cells to efficiently survey the host for cognate antigen. Non-mammalian jawed vertebrates lack lymph nodes but maintain similarly diverse T cell pools. Here, we exploit in vivo imaging of transparent zebrafish to investigate how T cells organize and survey for antigen in an animal devoid of lymph nodes. We find that naive-like T cells in zebrafish organize into a previously undescribed whole-body lymphoid network that supports streaming migration and coordinated trafficking through the host. This network has the cellular hallmarks of a mammalian lymph node, including naive T cells and CCR7-ligand expressing non-hematopoietic cells, and facilitates rapid collective migration. During infection, T cells transition to a random walk that supports antigen presenting cell interactions and subsequent activation. Our results reveal that T cells can toggle between collective migration and individual random walks to prioritize either large-scale trafficking or antigen search in situ. This novel lymphoid network thus facilitates whole-body T cell trafficking and antigen surveillance in the absence of a lymph node system.

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Real‐time imaging of inflammation and its resolution: It’s apparent because it’s transparent*

Cited by 15 publications

References 175 publications

PCSK9 Confers Inflammatory Properties to Extracellular Vesicles Released by Vascular Smooth Muscle Cells

PCSK9 Confers Inflammatory Properties to Extracellular Vesicles Released by Vascular Smooth Muscle Cells

Novel Epoxides of Soloxolone Methyl: An Effect of the Formation of Oxirane Ring and Stereoisomerism on Cytotoxic Profile, Anti-Metastatic and Anti-Inflammatory Activities In Vitro and In Vivo

A tessellated lymphoid network provides whole-body T cell surveillance in zebrafish

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