Selective Inhibition of NF-kB Activation and TNF-α Production in Macrophages by Red Blood Cell-Mediated Delivery of Dexamethasone
Abstract
Glucocorticoids are a widely used class of anti-inflammatory and immunosuppressive drugs, but their therapeutic use is limited by endocrine and metabolic side effects that they produce when given systemically. Since cells of the monocyte/macrophage lineage play an important role in the pathogenesis of several autoimmune and inflammatory diseases, a drug-delivery system which targets phagocytic cells was studied. We had previously demonstrated that dexamethasone, a potent glucocorticoid analogue, can be encapsulated in erythrocytes and selectively delivered to macrophages. In addition, lipopolysaccharide (LPS) stimulation of dexamethasone-targeted macrophages results in the suppression of TNF-alpha secretion. In this paper we demonstrate that the administration of dexamethasone to macrophages by means of opsonized red blood cells allows efficient interference with NF-kB activation. This NF-kB repression was in part mediated by induction of IkBalpha gene transcription and, as a consequence, by an increased rate of IkBalpha protein synthesis. Furthermore, NF-kB inactivation correlated with downmodulation of TNF-alpha mRNA expression, demonstrating that suppression of TNF-alpha production in dexamethasone-targeted cells occurs at the transcriptional level.
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Glucocorticoids tend to confer protective, anti-inflammatory effects.
“as GCs tend to confer protective, anti-inflammatory effects.36,41–43”
From Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases (2015) · cites this paper as [43]
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Negative regulation of nuclear factor-kappaB activation and function by glucocorticoids
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- Authors
- Crinelli, R., Antonelli, A., Bianchi, M., Gentilini, L., Scaramucci, S., & Magnani, M.
- Affiliations
- University of Urbino (IT)
- Corresponding author
- Magnani, Mauro
- Venue
- Blood Cells, Molecules, and Diseases
- Publisher
- Elsevier BV
- Published
- 2000-06
- Volume
- 26
- Issue
- 3
- Pages
- 211-222
- ISSN
- 1079-9796 (ISSN-L)
- OpenAlex
- W2132998265
- Cited by
- 84
- References
- 31
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 4 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 1 · 2012: 5
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood Cells Molecules and Diseases (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- dexamethasone, NF-κB activation, TNF-alpha production, macrophages, glucocorticoids, IκBα, lipopolysaccharide stimulation, transcriptional regulation, targeted drug delivery, inflammation
- MeSH terms
- Capsules, Dexamethasone, Drug Carriers, Erythrocytes, Gene Expression Regulation, Humans, Lipopolysaccharides, Macrophages, RNA, Messenger, Transcription, Genetic, Tumor Necrosis Factor-alpha, NF-kappa B, In Vitro Techniques
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