title: ADAM17 at the interface between inflammation and autoimmunity.
abstract: The discovery of the disintegrin and metalloproteinase 17 (ADAM17), originally identified as tumor necrosis factor-a converting enzyme (TACE) for its ability as sheddase of TNF-α inspired scientists to attempt to elucidate the molecular mechanisms underlying ADAM17 implication in diseased conditions. In recent years, it has become evident that this protease can modify many non matrix substrates, such as cytokines (e.g. TNF-α), cytokine receptors (e.g. IL-6R and TNF-R), ligands of ErbB (e.g. TGF-α and amphiregulin) and adhesion proteins (e.g. Lselectin and ICAM-1). Several recent studies have described experimental model system to better understand the role of specific signaling molecules, the interplay of different signals and tissue interactions in regulating ADAM17-dependent cleavage of most relevant substrates in inflammatory diseases. The central question is whether ADAM17 can influence the outcome of inflammation and if so, how it performs this regulation in autoimmunity, since inflammatory autoimmune diseases are often characterized by deregulated metalloproteinase activities. This review will explore the latest research on the influence of ADAM17 on the progression of inflammatory processes linked to autoimmunity and its role as modulator of inflammation.
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, Laboratory of Cell Biology, University of Bari Medical School, Bari, Italy. Electronic address: sabrina.lisi@uniba.it.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Lisi
authors.affiliation: Department of Interdisciplinary Medicine, Section of Rheumatology, University of Bari Medical School, Bari, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: D'Amore
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, Laboratory of Cell Biology, University of Bari Medical School, Bari, Italy. Electronic address: margherita.sisto@uniba.it.
authors.forename: Margherita
authors.initials: M
authors.lastname: Sisto
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072198:ADAM17 Protein; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D015398:Signal Transduction
chemical_list: D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
keywords: ADAM17; Autoimmunity; Inflammation; Metalloproteinases; Sjögren's syndrome