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Göteborgs universitets publikationer

Regulation of Toll-Like Receptors in the Choroid Plexus in the Immature Brain After Systemic Inflammatory Stimuli

Författare och institution:
Linnea Stridh (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Joakim Ek (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Xiaoyang Wang (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Holger Nilsson (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Carina Mallard (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi)
Publicerad i:
Translational Stroke Research, 4 ( 2 ) s. 220-227
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
The choroid plexus is the site of the blood–cerebrospinal fluid (CSF) barrier (BCSFB) and has also been considered as a possible route for peripheral immune signals and cells to transfer to the central nervous system. Infection/inflammation stimulates innate and subsequent adaptive immune responses via Toll-like receptors (TLRs). In this study, we have investigated the mRNA expression of TLRs, cytokines, and tight junction proteins in the choroid plexus in the immature brain after systemic inflammation, as well as accumulation of immune cells into the CSF. Specific ligands for TLR-1/2, TLR-3, and TLR-4 were administered to postnatal day 8 mice and mRNA expression for the targeted genes was examined in the choroid plexus. We found that mRNA for all four TLRs was detected in the choroid plexus under control conditions. Following immune stimulation, expression of all the TLRs was upregulated by their respective ligands, except for TLR-4 mRNA, which was downregulated by Pam3CSK4 (PAM; a TLR-1/2 ligand). In addition, we investigated BCSFB regulation after TLR stimulation and found that TLR-1/2 and TLR-4 activation was associated with changes in mRNA expression of the tight junction protein occludin in the choroid plexus. PAM induced choroid plexus transcription of TNF-α and resulted in the most dramatic increase in numbers of white blood cells in the CSF. The data suggest a possible mechanism whereby systemic inflammation stimulates TLRs in the choroid plexus, which may lead to disturbances in choroid plexus barrier function, as well as infiltration of immune cells through the plexus.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper ->
LPS, Poly I:C, Pam(3)CSK(4), Neonatal, Brain inflammation, Cerebrospinal fluid, White blood cells, cell-wall components, barrier permeability, tight junctions, white-matter, endothelial function, mice, cytokines, damage, injury, link
Postens nummer:
Posten skapad:
2013-04-26 09:48
Posten ändrad:
2013-10-11 17:52

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