Bone Marrow-Derived Macrophage Immortalization of LXR Nuclear Receptor-Deficient Cells

Ramón-Vázquez, Ana; Rosa, Juan Vladimir de la; Tabraue, Carlos; Castrillo, Antonio

doi:10.1007/978-1-4939-9130-3_6

Cited by 4 publications

(4 citation statements)

References 21 publications

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“…To prepare BMDMs, female C57/BL6 mice aged 8−10 weeks were used for the preparation of BMDMs according to a previously developed method. 43 In brief, all femurs and tibias of euthanized mice were surgically collected, and all muscle tissue was removed. After being disinfected with 70% alcohol for 2−5 min, the bones were rinsed with PBS, and their ends were cut off with scissors before their bone marrow cavities were repeatedly rinsed with PBS by using a syringe.…”

Section: Methodsmentioning

confidence: 99%

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Efferocytosis Nanoinhibitors to Promote Secondary Necrosis and Potentiate the Immunogenicity of Conventional Cancer Therapies for Improved Therapeutic Benefits

Wu,

Wang,

Yan

et al. 2023

ACS Nano

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Efferocytosis of apoptotic cancer cells by tumor-associated macrophages or other phagocytes is reported to promote tumor immunosuppression by preventing them from secondary necrosis, which would lead to the release of intracellular components and thus enhanced immunogenicity. Therefore, current apoptosis-inducing cancer treatments (e.g., chemotherapy and radiotherapy) are less satisfactory in eliciting antitumor immunity. Herein, a nanoparticulate inhibitor of efferocytosis is prepared by encapsulating BMS777607, a hydrophobic inhibitor of receptors in macrophages responsible for phosphatidylserine-dependent efferocytosis, with biocompatible poly(lactic-co-glycolic acid) and its amphiphilic derivatives. The yielded nano-BMS can inhibit the efferocytosis of apoptotic cancer cells, thus redirecting them to immunogenic secondary necrosis. As a result, intratumorally injected nano-BMS is capable of activating both innate and adaptive antitumor immunity to achieve greatly improved therapeutic responses, when synergized with nonimmunogenic chemotherapy by cisplatin, immunogenic chemotherapy by oxaliplatin, or radiotherapy by external beams. Moreover, we further demonstrate that the inhalation of nano-BMS could significantly promote the efficacy of cisplatin chemotherapy to suppress tumor lung metastases. Therefore, this study highlights a general strategy to potentiate the immunogenicity of different cancer treatments by suppressing efferocytosis-propelled tumor immunosuppression, showing tremendous clinical potential in rescuing existing cancer therapies for more effective treatment.

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Section: Methodsmentioning

confidence: 99%

“…To prepare BMDMs, female C57/BL6 mice aged 8–10 weeks were used for the preparation of BMDMs according to a previously developed method . In brief, all femurs and tibias of euthanized mice were surgically collected, and all muscle tissue was removed.…”

Section: Methodsmentioning

confidence: 99%

Efferocytosis Nanoinhibitors to Promote Secondary Necrosis and Potentiate the Immunogenicity of Conventional Cancer Therapies for Improved Therapeutic Benefits

Wu,

Wang,

Yan

et al. 2023

ACS Nano

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“…Several clones expressing LXR␣ or LXR␤ were isolated and tested for similar expression using anti-FLAG M2 antibody. A detailed protocol of this procedure is available through a recent review (59).…”

Section: Methodsmentioning

confidence: 99%

Common and Differential Transcriptional Actions of Nuclear Receptors Liver X Receptors α and β in Macrophages

Ramón-Vázquez

Rosa

Tabraue

et al. 2019

Molecular and Cellular Biology

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The liver X receptors α and β (LXRα and LXRβ) are oxysterol-activated transcription factors that coordinately regulate gene expression that is important for cholesterol and fatty acid metabolism. In addition to their roles in lipid metabolism, LXRs participate in the transcriptional regulation of macrophage activation and are considered potent regulators of inflammation. LXRs are highly similar, and despite notable exceptions, most of their reported functions are substantially overlapping. However, their individual genomic distribution and transcriptional capacities have not been characterized. Here, we report a macrophage cellular model expressing equivalent levels of tagged LXRs. Analysis of data from chromatin immunoprecipitation coupled with deep sequencing revealed that LXRα and LXRβ occupy both overlapping and exclusive genomic regulatory sites of target genes and also control the transcription of a receptor-exclusive set of genes. Analysis of genomic H3K27 acetylation and mRNA transcriptional changes in response to synthetic agonist or antagonist treatments revealed a putative mode of pharmacologically independent regulation of transcription. Integration of microarray and sequencing data enabled the description of three possible mechanisms of LXR transcriptional activation. Together, these results contribute to our understanding of the common and differential genomic actions of LXRs and their impact on biological processes in macrophages.

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“…Liver X receptors (LXRα and LXRβ), nuclear receptors controlling cholesterol metabolism and regulating macrophage differentiation, exhibit complex effects on apoptosis. While LXR activation enhances proinflammatory effects and impairs anti-inflammatory properties in macrophage colony-stimulating factor-dependent MoMFs [ 24 ], an abdominal macrophage study suggests that LXRα inhibits macrophage apoptosis by suppressing the endoplasmic reticulum stress-induced C/EBP homologous protein pathway [ 25 ]. The precise regulation of eukaryotic apoptosis during pathogen infection frequently constitutes a critical determinant in establishing a successful host–pathogen interaction [ 26 ].…”

Section: Macrophage Programmed Deathmentioning

confidence: 99%

Macrophage Perspectives in Liver Diseases: Programmed Death, Related Biomarkers, and Targeted Therapy

Qian,

Xiong,

Mao

et al. 2024

Biomolecules

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Macrophages, as important immune cells of the organism, are involved in maintaining intrahepatic microenvironmental homeostasis and can undergo rapid phenotypic changes in the injured or recovering liver. In recent years, the crucial role of macrophage-programmed cell death in the development and regression of liver diseases has become a research hotspot. Moreover, macrophage-targeted therapeutic strategies are emerging in both preclinical and clinical studies. Given the macrophages’ vital role in complex organismal environments, there is tremendous academic interest in developing novel therapeutic strategies that target these cells. This review provides an overview of the characteristics and interactions between macrophage polarization, programmed cell death, related biomarkers, and macrophage-targeted therapies. It aims to deepen the understanding of macrophage immunomodulation and molecular mechanisms and to provide a basis for the treatment of macrophage-associated liver diseases.

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Bone Marrow-Derived Macrophage Immortalization of LXR Nuclear Receptor-Deficient Cells

Cited by 4 publications

References 21 publications

Efferocytosis Nanoinhibitors to Promote Secondary Necrosis and Potentiate the Immunogenicity of Conventional Cancer Therapies for Improved Therapeutic Benefits

Efferocytosis Nanoinhibitors to Promote Secondary Necrosis and Potentiate the Immunogenicity of Conventional Cancer Therapies for Improved Therapeutic Benefits

Common and Differential Transcriptional Actions of Nuclear Receptors Liver X Receptors α and β in Macrophages

Macrophage Perspectives in Liver Diseases: Programmed Death, Related Biomarkers, and Targeted Therapy

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