Exploring New Inflammatory Biomarkers and Pathways during LPS-Induced M1 Polarization
Open accessAbstract
Identification of mediators triggering microglia activation and transference of noncoding microRNA (miRNA) into exosomes are critical to dissect the mechanisms underlying neurodegeneration. We used lipopolysaccharide- (LPS-) induced N9 microglia activation to explore new biomarkers/signaling pathways and to identify inflammatory miRNA (inflamma-miR) in cells and their derived exosomes. Upregulation of iNOS and MHC-II (M1-markers) and downregulation of arginase 1, FIZZ1 (M2-markers), and CX3CR1 (M0/M2 polarization) confirmed the switch of N9 LPS-treated cells into the M1 phenotype, as described for macrophages/microglia. Cells showed increased proliferation, activated TLR4/TLR2/NF-κ B pathway, and enhanced phagocytosis, further corroborated by upregulated MFG-E8. We found NLRP3-inflammasome activation in these cells, probably accounting for the increased extracellular content of the cytokine HMGB1 and of the MMP-9 we have observed. We demonstrate for the first time that the inflamma-miR profiling (upregulated miR-155 and miR-146a plus downregulated miR-124) in M1 polarized N9 cells, noticed by others in activated macrophages/microglia, was replicated in their derived exosomes, likely regulating the inflammatory response of recipient cells and dissemination processes. Data show that LPS-treated N9 cells behave like M1 polarized microglia/macrophages, while providing new targets for drug discovery. In particular, the study yields novel insights into the exosomal circulating miRNA during neuroinflammation important for emerging therapeutic approaches targeting microglia activation.
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Upon LPS stimulation, upregulation of miR-155 and miR-146a and downregulation of miR-124 (typical for M1 polarization) is accompanied by increased phagocytic activity.
“It was demonstrated that, typical for M1 polarization, upregulation of miR-155 and miR-146a, along with downregulation of miR-124 upon LPS stimulation, is accompanied with increased phagocytic activity.”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [242]
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- Authors
- Cunha, C., Gomes, C., Vaz, A. R., & Brites, D.
- Affiliations
- University of Lisbon (PT)
- Corresponding author
- Brites, Dora
- Venue
- Mediators of Inflammation
- Publisher
- Wiley
- Published
- 2016
- Volume
- 2016
- Pages
- 1-17
- ISSN
- 0962-9351 (ISSN-L)
- 1466-1861
- PMC
- PMC5209629
- OpenAlex
- W2567699986
- Cited by
- 153
- References
- 15
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 11 · 2023: 9 · 2022: 25 · 2021: 23 · 2020: 21 · 2019: 22 · 2018: 12 · 2017: 11 · 2016: 1
- FWCI
- 8.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Mediators of Inflammation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fundação para a Ciência e a Tecnologia (PTDC/SAU-FAR/118787/2010, UID/DTP/04138/2013, SFRH/BPD/76590/2011, SFRH/BD/91316/2012, SFRH/BD/102718/2014)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- microglial activation, M1 macrophage polarization, lipopolysaccharide, exosomal microRNAs, neuroinflammation, NLRP3 inflammasome, HMGB1, MMP-9, MFG-E8, miR-155, miR-146a, miR-124, inducible nitric oxide synthase, MHC class II, arginase-1, Fizz1, CX3CR1, neurodegeneration
- MeSH terms
- Animals, Arginase, Inflammation, Lipopolysaccharides, Macrophages, Phagocytosis, Phenotype, Biomarkers, Cytokines, Cell Death, Microglia, Matrix Metalloproteinase 9, Receptors, Interleukin-8A, HMGB1 Protein, MicroRNAs, Intercellular Signaling Peptides and Proteins, Cell Proliferation, Mice, Exosomes, Inflammasomes
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