title: ADAMTS-12 metalloprotease is necessary for normal inflammatory response.
abstract: ADAMTSs (a disintegrin and metalloprotease with thrombospondin domains) are a family of enzymes with both proteolytic and protein interaction functions, which have been implicated in distinct pathologies. In this work, we have investigated the putative role of ADAMTS-12 in inflammation by using a mouse model deficient in this metalloprotease. Control and mutant mice were subjected to different experimental conditions to induce colitis, endotoxic sepsis, and pancreatitis. We have observed that Adamts12-deficient mice exhibit more severe inflammation and a delayed recovery from these challenges compared with their wild-type littermates. These changes are accompanied by an increase in inflammatory markers including several cytokines, as assessed by microarray expression analysis and proteomic-based approaches. Interestingly, the clinical symptoms observed in Adamts12-deficient mice are also concomitant with an elevation in the number of neutrophils in affected tissues. Finally, isolation and in vitro culture of human neutrophils demonstrate that the presence of ADAMTS-12 induces neutrophil apoptosis. On the basis of these results, we propose that ADAMTS-12 is implicated in the inflammatory response by modulating normal neutrophil apoptosis.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain. amoncada@degradome.uniovi.es
authors.forename: Angela
authors.initials: A
authors.lastname: Moncada-Pazos
authors.forename: Alvaro J
authors.initials: AJ
authors.lastname: Obaya
authors.forename: María
authors.initials: M
authors.lastname: Llamazares
authors.forename: Ritva
authors.initials: R
authors.lastname: Heljasvaara
authors.forename: María F
authors.initials: MF
authors.lastname: Suárez
authors.forename: Enrique
authors.initials: E
authors.lastname: Colado
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
authors.forename: Santiago
authors.initials: S
authors.lastname: Cal
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Otín
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000071096:ADAMTS Proteins; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D003092:Colitis / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019446:Endotoxemia / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010195:Pancreatitis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C496252:ADAMTS12 protein, human; C550048:Adamts12 protein, mouse