title: TNF-alpha converting enzyme (TACE) protein expression in different clinical subtypes of multiple sclerosis.
abstract: Tumor necrosis factor (TNF)-alpha converting enzyme (TACE, also called ADAM17) is a key sheddase that releases TNF-alpha from its inactive cell-bound precursor. TACE protein expression levels in peripheral blood mononuclear cells were measured by Western blot analysis in 20 healthy controls and 80 multiple sclerosis (MS) patients before and after treatment with IFNbeta [20 patients with primary progressive (PP) MS, 20 patients with secondary progressive (SP) MS, and 40 patients with relapsing- remitting (RR) MS (20 patients during clinical remission and 20 patients in relapse)]. TNF-alpha serum levels were also measured by enzyme-linked immunoassay in the MS patients and healthy controls. TACE protein expression levels were lower in healthy controls and PPMS patients compared with SPMS patients and RRMS patient during clinical remission. No differences in TACE protein levels were observed between RRMS patients in relapse and during remission. TACE protein levels were increased in PPMS patients treated with IFNbeta. Serum TNF-alpha levels were higher in RRMS patients in relapse compared with RRMS patients during remission, and positive and negative correlations were found between TACE protein expression and serum TNF-alpha levels in RRMS patients during relapse and during remission respectively. These findings point to different regulatory mechanisms of the TACE-TNF-alpha pathway in the clinical MS subtypes and expand the role of TACE in MS pathogenesis.
authors.affiliation: Unitat de Neuroimmunologia Clínica, Hospital Universitari Vall d'Hebron, Escuela de Enfermeria 2a planta, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain. mcomabel@vhebron.net
authors.forename: Manuel
authors.initials: M
authors.lastname: Comabella
authors.forename: Cristina
authors.initials: C
authors.lastname: Romera
authors.forename: Montse
authors.initials: M
authors.lastname: Camiña
authors.forename: Hector
authors.initials: H
authors.lastname: Perkal
authors.forename: María A
authors.initials: MA
authors.lastname: Moro
authors.forename: Juan C
authors.initials: JC
authors.lastname: Leza
authors.forename: Ignacio
authors.initials: I
authors.lastname: Lizasoain
authors.forename: Mireia
authors.initials: M
authors.lastname: Castillo
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000328:Adult; D015153:Blotting, Western / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D016899:Interferon-beta / Q000627:therapeutic use; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000145:classification / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism*; D013223:Statistics as Topic
chemical_list: D007155:Immunologic Factors; D016899:Interferon-beta; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human