دورية أكاديمية
Lysosome-Dependent LXR and PPARδ Activation Upon Efferocytosis in Human Macrophages.
| العنوان: | Lysosome-Dependent LXR and PPARδ Activation Upon Efferocytosis in Human Macrophages. |
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| المؤلفون: | Mota AC; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany., Dominguez M; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany., Weigert A; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany., Snodgrass RG; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany., Namgaladze D; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany., Brüne B; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, Germany.; German Cancer Consortium (DKTK), Partner Site Frankfurt, Frankfurt, Germany.; Frankfurt Cancer Institute, Goethe-University Frankfurt, Frankfurt, Germany. |
| المصدر: | Frontiers in immunology [Front Immunol] 2021 May 07; Vol. 12, pp. 637778. Date of Electronic Publication: 2021 May 07 (Print Publication: 2021). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Apoptosis/*physiology , Liver X Receptors/*metabolism , Macrophages/*metabolism , PPAR gamma/*metabolism , Phagocytosis/*physiology, ATP Binding Cassette Transporter 1/metabolism ; Acyltransferases/metabolism ; Cell Line, Tumor ; Cholesterol/metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Jurkat Cells ; Liver X Receptors/genetics ; Lysosomes/metabolism ; PPAR gamma/genetics ; Phospholipases A2/metabolism ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase/metabolism ; RNA Interference ; RNA, Small Interfering/genetics ; Sterol Regulatory Element Binding Proteins/metabolism ; Transcription, Genetic/genetics ; Transcriptome/genetics |
| مستخلص: | Efferocytosis is critical for tissue homeostasis, as its deregulation is associated with several autoimmune pathologies. While engulfing apoptotic cells, phagocytes activate transcription factors, such as peroxisome proliferator-activated receptors (PPAR) or liver X receptors (LXR) that orchestrate metabolic, phagocytic, and inflammatory responses towards the ingested material. Coordination of these transcription factors in efferocytotic human macrophages is not fully understood. In this study, we evaluated the transcriptional profile of macrophages following the uptake of apoptotic Jurkat T cells using RNA-seq analysis. Results indicated upregulation of PPAR and LXR pathways but downregulation of sterol regulatory element-binding proteins (SREBP) target genes. Pharmacological inhibition and RNA interference pointed to LXR and PPARδ as relevant transcriptional regulators, while PPARγ did not substantially contribute to gene regulation. Mechanistically, lysosomal digestion and lysosomal acid lipase (LIPA) were required for PPAR and LXR activation, while PPARδ activation also demanded an active lysosomal phospholipase A Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Mota, Dominguez, Weigert, Snodgrass, Namgaladze and Brüne.) |
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| فهرسة مساهمة: | Keywords: apoptosis; efferocytosis; liver X receptor; macrophages; peroxisome proliferator-activated receptor |
| المشرفين على المادة: | 0 (ABCA1 protein, human) 0 (ATP Binding Cassette Transporter 1) 0 (Liver X Receptors) 0 (NR1H3 protein, human) 0 (PDK4 protein, human) 0 (PPAR gamma) 0 (PPARG protein, human) 0 (Pyruvate Dehydrogenase Acetyl-Transferring Kinase) 0 (RNA, Small Interfering) 0 (Sterol Regulatory Element Binding Proteins) 97C5T2UQ7J (Cholesterol) EC 2.3.- (Acyltransferases) EC 3.1.1.4 (Phospholipases A2) EC 3.1.1.4 (phospholipase A2, group XV) |
| تواريخ الأحداث: | Date Created: 20210524 Date Completed: 20210923 Latest Revision: 20210923 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8137840 |
| DOI: | 10.3389/fimmu.2021.637778 |
| PMID: | 34025647 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2021.637778 |