Acta Neuropathologica: IL-1 promotes autoimmune neuroinflamed by inhibiting hemoglobin oxytocin-1 in the hemoglobin-1 of the blood-brain barrier.

Inflammatory disease multiple sclerosis (MS) and its animal model experimental autoimmune encephalopathy (EAE) are characterized by peripheral immune cells immersed in the central nervous system (CNS), which eventually leads to demyelination and axon damage to the brain and spinal cord.
cell immersion in MS/EAE is the result of local blood-brain barrier (BBB) destruction, which allows exocytes and molecules to flow unstoetically.
BBB is a tightly regulated vascular barrier consisting of special endodertic cells (ECs) that are tightly connected and bonded between cells to control the flow of cells and molecules on BBB.
In MS and EAE, the disorder of these connecting proteins is associated with the increase in cell-to-cell adhesion molecules -1 (Icam-1) and vascular adhesion molecules-1 (Vcam-1) associated with peripheral cell adhesion and migration to the central nervous system.
-inflammatory cytokine lecytokine 1 (IL-1) is closely related to the pathogenesis of MS and EEA.
in this paper, we used mice missing their signaling subject IL-1R1 to study the role of IL-1 signals in EEA development in BBB-ECs, astrocytes, and small glial cells.
we found that IL-1 signals in small glial cells and assailant glial cells were redundant in the occurrence of EEA, while the absence of IL-1R1 in BBB-ECs significantly improved the severity of the disease.
the expression of the adhesive molecules Vcam-1, Icam-1, and the chemical factor-dependent Darc in BBB-ECs, all of which have been shown to promote CNS-specific inflammatory responses.
contrary, the IL-1R1 signal inhibits the expression of the stress-reactive hemolybin breakdown metabolic enzyme hemoxygen oxygenase-1 (HO-1) in BBB-ECs, and promotes disease progression through mechanisms associated with regulatory expression disorders associated with the IL-1 response genes Vcam1, Icam1, and Ackr1 (Darc).
the mechanism, our data emphasize the functional crosstalk of BBB-EC IL-1 signals and HO-1, and control the transcription of downstream inflammatory genes, thus promoting the pathogenesis of autoimmune neuroinflamm.
method: In order to separate CNS-EC, the mice were executed according to the above method and perfusion by heart.
anatomic CNS tissue was digested for 30 minutes at 37 degrees C with a 2mg/ml papaya protease (Sigma-Aldrich) solution containing 40 mg/ml DNase I.
incubating, the tissue is mechanically homogened using a mild MACS dissograph (Miltenyi).
the resulting cell suspension is filtered through a 70 m cell filter and centrifuged at 15 degrees C at a 20% Percoll gradient for 30 minutes, 300 x g.
particles containing a mixture of CNS cells are used for fluid cytometic staining.
in general, our research supports functional crosstalk between the NF-B and Nrf2/HO-1 paths.
, however, the identification of effective and specific Nrf2 activators or their inhibitors targeted for the treatment of MS and other inflammatory diseases requires further detailed study.
we believe that a precise understanding of this crosstalk will help to target and manipulate the balance between Nrf2 and NF-B signals, which ultimately represents a promising way to improve MS treatment.
Hauptmann, J., Johann, L., Marini, F. et al. Interleukin-1 promotes autoimmune neuroinflammation by suppressing endothelial heme oxygenase-1 at the blood-brain barrier. Acta Neuropathol 140, 549-567 (2020). MedSci Original Source: MedSci Original Copyright Notice: All text, images and audio and video materials on this website that indicate "Source: Mets Medicine" or "Source: MedSci Originals" are owned by Mets Medicine and are not authorized to be reproduced by any media, website or individual, and are authorized to be reproduced with the words "Source: Mets Medicine".
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