Enhancing arginase 2 expression using target site blockers as a strategy to modulate macrophage phenotype

Santi, Chiara De; Nally, Frances K.; Afzal, Remsha; Duffy, Conor P.; Fitzsimons, Stephen; Annett, Stephanie; Robson, Tracy; Dowling, Jennifer K.; Cryan, Sally‐Ann; McCoy, Claire E.

doi:10.1016/j.omtn.2022.08.004

Cited by 8 publications

(5 citation statements)

References 44 publications

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“…Transcription factor Fra-1 reemerges M1 macrophages by silencing Arg-1 to enhance inflammation [ 277 ]. Arg-2, another enzyme involved in L-arginine metabolism, modulates mitochondrial dynamics to upregulate OXPHOS, polarizing M1 macrophages to M2 phenotype [ 278 , 279 ]. Jiang et al [ 190 ] engineered a liver-inspired polyetherketoneketone (PEKK) scaffold with a thickness of 30 μm by femtosecond laser etching technology and sulfonation reaction.…”

Section: Nm-mediated Macrophage Activity Visualization and Fate Tailo...mentioning

confidence: 99%

Nanomaterial-Based Repurposing of Macrophage Metabolism and Its Applications

Meng,

He,

Han

et al. 2024

Nano-Micro Lett.

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Macrophage immunotherapy represents an emerging therapeutic approach aimed at modulating the immune response to alleviate disease symptoms. Nanomaterials (NMs) have been engineered to monitor macrophage metabolism, enabling the evaluation of disease progression and the replication of intricate physiological signal patterns. They achieve this either directly or by delivering regulatory signals, thereby mapping phenotype to effector functions through metabolic repurposing to customize macrophage fate for therapy. However, a comprehensive summary regarding NM-mediated macrophage visualization and coordinated metabolic rewiring to maintain phenotypic equilibrium is currently lacking. This review aims to address this gap by outlining recent advancements in NM-based metabolic immunotherapy. We initially explore the relationship between metabolism, polarization, and disease, before delving into recent NM innovations that visualize macrophage activity to elucidate disease onset and fine-tune its fate through metabolic remodeling for macrophage-centered immunotherapy. Finally, we discuss the prospects and challenges of NM-mediated metabolic immunotherapy, aiming to accelerate clinical translation. We anticipate that this review will serve as a valuable reference for researchers seeking to leverage novel metabolic intervention-matched immunomodulators in macrophages or other fields of immune engineering.

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Section: Nm-mediated Macrophage Activity Visualization and Fate Tailo...mentioning

confidence: 99%

Nanomaterial-Based Repurposing of Macrophage Metabolism and Its Applications

Meng,

He,

Han

et al. 2024

Nano-Micro Lett.

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“… 51 Our previous work in vivo and in murine macrophages demonstrated that a TSB designed to inhibit miR-155 interaction with Arg2 was an effective strategy to enhance Arg2, which led to the suppression of pro-inflammatory signaling. 31 Arg2 activation by liver X receptor agonists in macrophages inhibited nitrite production in response to inflammatory stimuli. 52 In addition, TSBs designed to target miR-155 interaction with RhoA and human antigen receptor were successfully used in the context of cancer.…”

Section: Discussionmentioning

confidence: 96%

“… 30 Most recently, we have demonstrated that a TSB targeting the interaction of miR-155 and Arg2 is effective in enhancing Arg2 expression and inhibiting pro-inflammatory cytokine secretion both in vitro , in murine macrophages, and in vivo , in a murine model of LPS-induced acute inflammation. 31 However, much of this research was performed using murine models and cell lines, and the implications of modulating Arg2 need to be evaluated in human primary macrophages to be therapeutically viable. In this study, our focus was to employ TSBs to upregulate Arg2 in unstimulated human monocyte-derived macrophages (MDMs) and to investigate the macrophage response to a pro-inflammatory stimulus by assessing cytokines and markers of inflammation in conjunction with proteomic analysis.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of pro-inflammatory signaling in human primary macrophages by enhancing arginase-2 via target site blockers

Fitzsimons,

Muñoz-San Martín,

Nally

et al. 2023

Molecular Therapy - Nucleic Acids

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“…1 , 2 ) [ 30 , 106 ]. MiR-155 engendered AT1R downregulation and reduced membrane availability coaxes a RAAS cardioprotective state [ 73 ], avails increased eNOS/NO pathway activation [ 47 , 157 ], the latter further potentiated by Arg2 repression [ 80 , 119 , 158 ], leading to increased NO-bioavailability and impaired AT1R-mediated endocytosis, SARS-CoV-2 replication, and cell entry (Fig. 2 ) [ 44 , 102 ].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Beauty and the beast: host microRNA-155 versus SARS-CoV-2

Papadopoulos

Papadopoulou

2023

Human Cell

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Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection in the young and healthy usually results in an asymptomatic or mild viral syndrome, possibly through an erythropoietin (EPO)-dependent, protective evolutionary landscape. In the old and in the presence of co-morbidities, however, a potentially lethal coronavirus disease 2019 (COVID-19) cytokine storm, through unrestrained renin-angiotensin aldosterone system (RAAS) hyperactivity, has been described. Multifunctional microRNA-155 (miR-155) elevation in malaria, dengue virus (DENV), the thalassemias, and SARS-CoV-1/2, plays critical antiviral and cardiovascular roles through its targeted translational repression of over 140 genes. In the present review, we propose a plausible miR-155-dependent mechanism whereby the translational repression of AGRT1 , Arginase-2 and Ets-1 , reshapes RAAS towards Angiotensin II (Ang II) type 2 (AT2R)-mediated balanced, tolerable, and SARS-CoV-2-protective cardiovascular phenotypes. In addition, it enhances EPO secretion and endothelial nitric oxide synthase activation and substrate availability, and negates proinflammatory Ang II effects. Disrupted miR-155 repression of AT1R + 1166C-allele, significantly associated with adverse cardiovascular and COVID-19 outcomes, manifests its decisive role in RAAS modulation. BACH1 and SOCS1 repression creates an anti-inflammatory and cytoprotective milieu, robustly inducing antiviral interferons. MiR-155 dysregulation in the elderly, and in comorbidities, allows unimpeded RAAS hyperactivity to progress towards a particularly aggressive COVID-19 course. Elevated miR-155 in thalassemia plausibly engenders a favorable cardiovascular profile and protection against malaria, DENV, and SARS-CoV-2. MiR-155 modulating pharmaceutical approaches could offer novel therapeutic options in COVID-19.

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Enhancing arginase 2 expression using target site blockers as a strategy to modulate macrophage phenotype

Cited by 8 publications

References 44 publications

Nanomaterial-Based Repurposing of Macrophage Metabolism and Its Applications

Nanomaterial-Based Repurposing of Macrophage Metabolism and Its Applications

Inhibition of pro-inflammatory signaling in human primary macrophages by enhancing arginase-2 via target site blockers

Beauty and the beast: host microRNA-155 versus SARS-CoV-2

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