title: IL-1β down-regulates ADAMTS-13 mRNA expression in cells of the central nervous system.
abstract: ADAMTS-13 is the Von Willebrand factor (vWF) cleaving protease, responsible for the cleavage and down-regulation of the pro-thrombotic properties of ultra large VWF multimers. It is expressed predominantly by the hepatic stellate cells of the liver, but is also found to be expressed in other tissues, including brain. Reduced ADAMTS-13 is associated with a variety of thrombotic microangiopathies. Since the cellular origin and regulation of ADAMTS-13 expression in the brain is unknown, we aimed to investigate this in four different central nervous system (CNS)-derived cell lines, SHSY-5Y (human neuroblastoma), U373 (human astroglioma), CHME-3 (human foetal microglia) and hCMEC/D3 (adult human brain endothelial cells). All cell lines expressed ADAMTS-13 mRNA constitutively with neuroblastoma cells showing the highest expression. Interleukin (IL)-1β down-regulated ADAMTS-13 mRNA expression in astroglioma cells and microglial cells whereas TNF and IL-6 treatment showed no significant differences in ADAMTS-13 mRNA expression in any cell line tested. ADAMTS-13 protein expression was reduced in a dose-dependent manner only in astroglioma cells following stimulation by IL-1β. The ability of IL-1β to significantly reduce ADAMTS-13 mRNA expression in human microglia and astroglioma cells suggests a role in the haemostasis of the local microenvironment under inflammatory conditions. This is the first report of ADAMTS-13 expression in cells of the CNS; however, its function remains to be determined.
authors: Biomedical Research Centre, Faculty of Health and Wellbeing, Sheffield Hallam University, Howard Street, Sheffield, S1 1WB, UK. g.a.frentzou@leeds.ac.uk
authors: G Alkistis
authors: GA
authors: Frentzou
authors: Claire
authors: C
authors: Bradford
authors: Kirsty A
authors: KA
authors: Harkness
authors: Gail
authors: G
authors: Haddock
authors: M Nicola
authors: MN
authors: Woodroofe
authors: Alison K
authors: AK
authors: Cross
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis / Q000235:genetics*; D000071120:ADAMTS13 Protein; D000328:Adult; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D001254:Astrocytoma / Q000201:enzymology / Q000473:pathology; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D002460:Cell Line / Q000201:enzymology; D045744:Cell Line, Tumor / Q000201:enzymology; D015536:Down-Regulation / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009447:Neuroblastoma / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human