| RRC ID |
86316
|
| Author |
Brandl S, Yu Q, Hagenbuchner J, Endmayr V, Höftberger R, Bradl M, Reindl M.
|
| Title |
Inflammatory transcriptomic signatures in a human cellular NMOSD model reveal upregulation of NF-κB and IL6 pathways.
|
| Journal |
Sci Rep
|
| Abstract |
Neuromyelitis optica spectrum disorder (NMOSD) is a rare neurological autoimmune disease caused by autoantibodies targeting the astrocytic water channel aquaporin-4 (AQP4). Binding to AQP4 initiates the activation of innate immune components, especially the complement system. Both in-vivo and in-vitro models have been developed to study the molecular pathophysiology of NMOSD. Our study aimed to characterize the molecular response of four human cell lines (AQP4-ECFP expressing U-87MG glioblastoma cells, U-87MG expressing only ECFP, HEK293 cells expressing AQP4-EmGFP, and human primary astrocytes) to a treatment with AQP4 antibody E5415A and human complement. Complement-dependent cytotoxicity was induced by this treatment in AQP4-expressing cells by the terminal complement pathway. Transcriptomic profiles of the in-vitro U-87MG-AQP4-ECFP model and an in-vivo rat model shared a proinflammatory shift towards NF-κB and interleukin-6 pathways. These findings were confirmed at both the mRNA and protein levels, and treatment with serum samples from AQP4 antibody seropositive NMOSD patients resulted in a similar response. Additionally, NF-κB upregulation was shown by immunohistochemistry in medulla oblongata lesions of NMOSD patients. In conclusion, interleukin-6 and NF-κB pathways play a key role in inflammation caused by the activation of the terminal complement pathway in a human cellular model of NMOSD using U-87MG-AQP4-ECFP cells.
|
| Volume |
15(1)
|
| Pages |
43346
|
| Published |
2025-12-8
|
| DOI |
10.1038/s41598-025-27335-9
|
| PII |
10.1038/s41598-025-27335-9
|
| PMID |
41361218
|
| PMC |
PMC12686536
|
| MeSH |
Animals
Aquaporin 4 / genetics
Aquaporin 4 / immunology
Aquaporin 4 / metabolism
Astrocytes / metabolism
Cell Line, Tumor
Female
HEK293 Cells
Humans
Inflammation* / genetics
Interleukin-6* / genetics
Interleukin-6* / metabolism
Male
NF-kappa B* / genetics
NF-kappa B* / metabolism
Neuromyelitis Optica* / genetics
Neuromyelitis Optica* / immunology
Neuromyelitis Optica* / metabolism
Neuromyelitis Optica* / pathology
Rats
Signal Transduction
Transcriptome*
Up-Regulation
|
| IF |
3.998
|
| Resource |
| Human and Animal Cells |
AQP4(E5415A-1H6-68)(RCB4883) |
