Sphingosine Kinase 1 and Sphingosine 1-Phosphate Receptor 3 Are Upregulated in Astrocytes under Inflammation
Author Information
Author(s): Iris Fischer, Chantal Alliod, Nicolas Martinier, Jia Newcombe, Corinne Brana, Sandrine Pouly
Primary Institution: Merck Serono International, Geneva, Switzerland
Hypothesis
The role of S1P receptor subtype 3 (S1P3) signaling and SphK1 in activated rat astrocytes has not been defined.
Conclusion
The SphK1/S1P3 signaling axis is upregulated in activated astrocytes, which may contribute to neuroinflammation and potentially aid in remyelination.
Supporting Evidence
- S1P3 and SphK1 expression was significantly increased in reactive astrocytes in MS lesions.
- LPS treatment led to a marked upregulation of S1P3 and SphK1 in primary rat astrocytes.
- Inhibition of SphK1 reduced LPS-induced astrocyte migration.
- S1P3 signaling was shown to enhance CXCL1 release in activated astrocytes.
Takeaway
When brain cells called astrocytes get activated by inflammation, they produce more of a signaling molecule that can help or hurt the brain.
Methodology
Immunohistochemistry, qPCR, Western blotting, and scratch assays were used to analyze astrocyte activation and signaling.
Potential Biases
Potential bias due to the involvement of authors from a pharmaceutical company.
Limitations
The study primarily used rat models, which may not fully represent human conditions.
Participant Demographics
Samples from 8 MS lesions from 7 patients, average age 51 years.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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