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Cited by 112Neuroinflammation and Neurodegeneration MechanismsSphingolipid Metabolism and SignalingPain Mechanisms and Treatments

1-Oleyl-lysophosphatidic acid (LPA) promotes polarization of BV-2 and primary murine microglia towards an M1-like phenotype

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Plastira, Ioanna, Bernhart, Eva, Goeritzer, Madeleine, Reicher, Helga, Kumble, Vishwanath Bhat, Kogelnik, Nora, Wintersperger, Andrea, Hammer, Astrid +6 more·2016·Journal of Neuroinflammation
DOI 10.1186/s12974-016-0701-9PMC PMC5002165
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Abstract

BACKGROUND: Microglia, the immunocompetent cells of the CNS, rapidly respond to brain injury and disease by altering their morphology and phenotype to adopt an activated state. Microglia can exist broadly between two different states, namely the classical (M1) and the alternative (M2) phenotype. The first is characterized by the production of pro-inflammatory cytokines/chemokines and reactive oxygen and/or nitrogen species. In contrast, alternatively activated microglia are typified by an anti-inflammatory phenotype supporting wound healing and debris clearance. The objective of the present study was to determine the outcome of lysophosphatidic acid (LPA)-mediated signaling events on microglia polarization. METHODS: LPA receptor expression and cyto-/chemokine mRNA levels in BV-2 and primary murine microglia (PMM) were determined by qPCR. M1/M2 marker expression was analyzed by Western blotting, immunofluorescence microscopy, or flow cytometry. Cyto-/chemokine secretion was quantitated by ELISA. RESULTS: BV-2 cells express LPA receptor 2 (LPA2), 3, 5, and 6, whereas PMM express LPA1, 2, 4, 5, and 6. We show that LPA treatment of BV-2 and PMM leads to a shift towards a pro-inflammatory M1-like phenotype. LPA treatment increased CD40 and CD86 (M1 markers) and reduced CD206 (M2 marker) expression. LPA increased inducible nitric oxide synthase (iNOS) and COX-2 levels (both M1), while the M2 marker Arginase-1 was suppressed in BV-2 cells. Immunofluorescence studies (iNOS, COX-2, Arginase-1, and RELMα) extended these findings to PMM. Upregulation of M1 markers in BV-2 and PMM was accompanied by increased cyto-/chemokine transcription and secretion (IL-1β, TNFα, IL-6, CCL5, and CXCL2). The pharmacological LPA5 antagonist TCLPA5 blunted most of these pro-inflammatory responses. CONCLUSIONS: LPA drives BV-2 and PMM towards a pro-inflammatory M1-like phenotype. Suppression by TCLPA5 indicates that the LPA/LPA5 signaling axis could represent a potential pharmacological target to interfere with microglia polarization in disease.

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  • The absence of ramified microglial cells may stem from BV-2 cells being a transformed microglia cell line with different morphology compared to microglia directly isolated from animals.

    “This may stem from the BV-2 cells, a transformed microglia cell line with differed morphology compared to microglia directly isolated from the animals,48 which was reported previously.51–53”

    From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [51]

    The Methods sections (page unavailable) identify BV-2 as a murine microglial cell line and describe primary microglia isolated from mice. The Results discuss morphology in both, but do not say that BV-2 cells are transformed, that their morphology differs from primary microglia, or that this explains an absence of ramified cells. (LLM, conf=0.84)

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Authors
Plastira, I., Bernhart, E., Goeritzer, M., Reicher, H., Kumble, V. B., Kogelnik, N., Wintersperger, A., Hammer, A., Schlager, S., Jandl, K., Heinemann, A., Kratky, D., Malle, E., & Sattler, W.
Affiliations
Medical University of Graz (AT)
Corresponding author
Sattler, Wolfgang
ORCID
Venue
Journal of Neuroinflammation
Publisher
Springer Science and Business Media LLC
Published
2016-08-26
Volume
13
Issue
1
Pages
205-205
ISSN
1742-2094 (ISSN-L)
DOI
10.1186/s12974-016-0701-9
PMC
PMC5002165
OpenAlex
W2508271242
Cited by
112
References
5
Citations by year
2026: 5 · 2025: 11 · 2024: 19 · 2023: 13 · 2022: 11 · 2021: 18 · 2020: 16 · 2019: 8 · 2018: 4 · 2017: 6 · 2016: 1
FWCI
3.47
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Journal of Neuroinflammation (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Austrian Science Fund (DK-MOLIN W1241, DK-MCD W1226)
  • BioTechMed Graz
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
lysophosphatidic acid, microglial polarization, M1 macrophage phenotype, M2 phenotype, BV-2 cells, inflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase-2, arginase-1, RELMα, CD40, CD86, CD206, chemokines, neuroinflammation
MeSH terms
Actins, Analysis of Variance, Animals, Animals, Newborn, Cells, Cultured, Cerebral Cortex, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Lysophospholipids, RNA, Messenger, Time Factors, Cytokines, Cell Polarity, Reactive Oxygen Species, Microglia, Receptors, Lysophosphatidic Acid, Mice, Nitric Oxide Synthase Type II

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