title: Pro-inflammatory cytokines modulate matrix metalloproteinase secretion and organic anion transport at the blood-cerebrospinal fluid barrier.
abstract: Neuroinflammation and neuroinfection trigger cytokine-mediated responses that include an increase in the cerebrospinal fluid (CSF) levels of pro-inflammatory matrix metalloproteinases (MMPs) and organic anions such as leukotrienes and prostaglandins. The choroid plexus (CP) epithelium forming the interface between the blood and the CSF regulates the CSF concentration of bioactive organic anions and is involved in neuro-immune regulation. We demonstrated that both fourth and lateral ventricle CPs are a source of pro- and active MMP-2 and MMP-9 in the brain. Using a cellular model of the blood-CSF barrier, we showed that a pro-inflammatory cytokine treatment leads to an increase in the choroidal MMP secretion at either the apical or the basolateral membrane, depending on the ventricular origin of the choroidal cells. This effect was not concomitant with an alteration in the structural blood-CSF barrier. Neither was the pool of antioxidant sulfhydryls in the choroidal cells challenged. In contrast, the efficiency of the choroidal epithelium to clear the CSF from organic anions was highly reduced. Thus, during inflammation, the CPs could be one source of MMPs found in the CSF facilitate leucocyte migration by secreting MMPs into the choroidal stroma, and promote the inflammatory process by failing in its ability to clear deleterious compounds from the brain.
authors.affiliation: Unité INSERM 433, Faculté de Médecine Laennec, Lyon, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Strazielle
authors.forename: Seng Thuon
authors.initials: ST
authors.lastname: Khuth
authors.forename: Audrey
authors.initials: A
authors.lastname: Murat
authors.forename: Aurélie
authors.initials: A
authors.lastname: Chalon
authors.forename: Pascale
authors.initials: P
authors.lastname: Giraudon
authors.forename: Marie Françoise
authors.initials: MF
authors.lastname: Belin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Ghersi-Egea
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D018836:Inflammation Mediators / Q000502:physiology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000378:metabolism*; D051381:Rats
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D027361:Organic Anion Transporters; D020782:Matrix Metalloproteinases