title: Expression of ADAMs and their inhibitors in sputum from patients with asthma.
abstract: ADAMs (a disintegrin and metalloprotease) constitute a family of cell surface proteins containing disintegrin and metalloprotease domains which associate features of adhesion molecules and proteases. ADAMTSs (a disintegrin and metalloprotease with thrombospondin motifs) bear thrombospondin type I motifs in C-terminal extremity, and most of them are secreted proteins. Because genetic studies have shown that ADAM-33 gene polymorphisms are associated with asthma, we designed this study to assess mRNA expression profile of several ADAM and ADAMTS proteases in sputum from patients with asthma and to investigate the relationship between expression of these proteases and asthma-associated inflammation and airway obstruction. mRNA expression profile of selected ADAM and ADAMTS proteinases (ADAM-8, -9, -10, -12, -15, -17, and -33; ADAMTS-1, -2, -15, -16, -17, -18, and -19), their physiological inhibitors TIMP-1 and TIMP-3, and RECK, a membrane-anchored MMP activity regulator, was obtained by RT-PCR analysis performed on cells collected by sputum induction from 21 patients with mild to moderate asthma and 17 healthy individuals. mRNA levels of ADAM-8, ADAM-9, ADAM-12, TIMP-1, and TIMP-3 were significantly increased, whereas mRNA levels coding for ADAMTS-1, ADAMTS-15, and RECK were significantly decreased in patients with asthma compared with control patients. ADAM-8 expression was negatively correlated with the forced expiratory volume at the first second (FEV(1)) (r = -0.57, P < 0.01), whereas ADAMTS-1 and RECK expressions were positively correlated to FEV(1) (r = 0.45, P < 0.05, and r = 0.55, P = 0.01, respectively). We conclude that expression of ADAMs and ADAMTSs and their inhibitors is modulated in airways from patients with asthma and that these molecules may play a role in the pathogenesis of asthma.
authors.affiliation: Department of Biology of Tumours, Center for Biomedical Integrative Genoproteomics, CHU Liège, University of Liege, Belgium.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Paulissen
authors.forename: Natacha
authors.initials: N
authors.lastname: Rocks
authors.forename: Florence
authors.initials: F
authors.lastname: Quesada-Calvo
authors.forename: Philippe
authors.initials: P
authors.lastname: Gosset
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.forename: Agnès
authors.initials: A
authors.lastname: Noel
authors.forename: Renaud
authors.initials: R
authors.lastname: Louis
authors.forename: Didier D
authors.initials: DD
authors.lastname: Cataldo
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics* / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D002452:Cell Count; D005260:Female; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013183:Sputum / Q000166:cytology / Q000378:metabolism*; D013347:Subcellular Fractions; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics* / Q000378:metabolism
chemical_list: C069667:FEV1 lipopolysaccharide; D058851:GPI-Linked Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C115460:RECK protein, human; D012333:RNA, Messenger; D017455:Receptors, IgE; D019714:Tissue Inhibitor of Metalloproteinases; D051722:ADAM Proteins