Interleukin-1 promotes autoimmune neuroinflammation by suppressing endothelial heme oxygenase-1 at the blood–brain barrier

  1. Hauptmann, Judith
  2. Johann, Lisa
  3. Marini, Federico
  4. Kitic, Maja
  5. Colombo, Elisa
  6. Mufazalov, Ilgiz A.
  7. Krueger, Martin
  8. Karram, Khalad
  9. Moos, Sonja
  10. Wanke, Florian
  11. Kurschus, Florian C.
  12. Klein, Matthias
  13. Cardoso, Silvia
  14. Strauß, Judith
  15. Bolisetty, Subhashini
  16. Lühder, Fred
  17. Schwaninger, Markus
  18. Binder, Harald
  19. Bechman, Ingo
  20. Bopp, Tobias
  21. Agarwal, Anupam
  22. Soares, Miguel P.
  23. Regen, Tommy
  24. Waisman, Ari ORCID logo

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WeightNameValue
1000 Titel
  • Interleukin-1 promotes autoimmune neuroinflammation by suppressing endothelial heme oxygenase-1 at the blood–brain barrier
1000 Autor/in
  1. Hauptmann, Judith |
  2. Johann, Lisa |
  3. Marini, Federico |
  4. Kitic, Maja |
  5. Colombo, Elisa |
  6. Mufazalov, Ilgiz A. |
  7. Krueger, Martin |
  8. Karram, Khalad |
  9. Moos, Sonja |
  10. Wanke, Florian |
  11. Kurschus, Florian C. |
  12. Klein, Matthias |
  13. Cardoso, Silvia |
  14. Strauß, Judith |
  15. Bolisetty, Subhashini |
  16. Lühder, Fred |
  17. Schwaninger, Markus |
  18. Binder, Harald |
  19. Bechman, Ingo |
  20. Bopp, Tobias |
  21. Agarwal, Anupam |
  22. Soares, Miguel P. |
  23. Regen, Tommy |
  24. Waisman, Ari |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-07-11
1000 Erschienen in
1000 Quellenangabe
  • 140(4):549-567
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00401-020-02187-x |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498485/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • The proinflammatory cytokine interleukin 1 (IL-1) is crucially involved in the pathogenesis of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Herein, we studied the role of IL-1 signaling in blood-brain barrier (BBB) endothelial cells (ECs), astrocytes and microglia for EAE development, using mice with the conditional deletion of its signaling receptor IL-1R1. We found that IL-1 signaling in microglia and astrocytes is redundant for the development of EAE, whereas the IL-1R1 deletion in BBB-ECs markedly ameliorated disease severity. IL-1 signaling in BBB-ECs upregulated the expression of the adhesion molecules Vcam-1, Icam-1 and the chemokine receptor Darc, all of which have been previously shown to promote CNS-specific inflammation. In contrast, IL-1R1 signaling suppressed the expression of the stress-responsive heme catabolizing enzyme heme oxygenase-1 (HO-1) in BBB-ECs, promoting disease progression via a mechanism associated with deregulated expression of the IL-1-responsive genes Vcam1, Icam1 and Ackr1 (Darc). Mechanistically, our data emphasize a functional crosstalk of BBB-EC IL-1 signaling and HO-1, controlling the transcription of downstream proinflammatory genes promoting the pathogenesis of autoimmune neuroinflammation.
1000 Sacherschließung
lokal Encephalomyelitis, Autoimmune, Experimental/enzymology [MeSH]
lokal Inflammation/immunology [MeSH]
lokal Interleukin-1
lokal Mice, Inbred C57BL [MeSH]
lokal Blood–brain barrier
lokal Interleukin-1/immunology [MeSH]
lokal Encephalomyelitis, Autoimmune, Experimental/immunology [MeSH]
lokal Animals [MeSH]
lokal Endothelial Cells/enzymology [MeSH]
lokal Signal Transduction/immunology [MeSH]
lokal Autoimmunity
lokal Blood-Brain Barrier/immunology [MeSH]
lokal Experimental autoimmune encephalomyelitis (EAE)
lokal Mice [MeSH]
lokal Heme Oxygenase-1/metabolism [MeSH]
lokal Heme oxygenase-1 (HO-1)
lokal Original Paper
lokal Blood-Brain Barrier/enzymology [MeSH]
lokal Gene Expression Regulation/immunology [MeSH]
1000 Liste der Beteiligten
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1000 Erstellt am 2023-11-17T02:33:37.626+0100
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