title: Structural basis of blocking integrin activation and deactivation for anti-inflammation.
abstract: Integrins mediate leukocyte accumulation to the sites of inflammation, thereby enhancing their potential as an important therapeutic target for inflammatory disorders. Integrin activation triggered by inflammatory mediators or signaling pathway is a key step to initiate leukocyte migration to inflamed tissues; however, an appropriately regulated integrin deactivation is indispensable for maintaining productive leukocyte migration. While typical integrin antagonists that block integrin activation target the initiation of leukocyte migration, a novel class of experimental compounds has been designed to block integrin deactivation, thereby perturbing the progression of cell migration. Current review discusses the mechanisms by which integrin is activated and subsequently deactivated by focusing on its structure-function relationship.
authors.affiliation: Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Mie, 514-8507, Japan. epark@doc.medic.mie-u.ac.jp.|Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan. epark@doc.medic.mie-u.ac.jp.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Park
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan. yukiy@ims.u-tokyo.ac.jp.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yuki
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan. kiyono@ims.u-tokyo.ac.jp.|International Research and Development Center for Mucosal Vaccine, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan. kiyono@ims.u-tokyo.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
authors.affiliation: Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Mie, 514-8507, Japan. shimaoka@doc.medic.mie-u.ac.jp.
authors.forename: Motomu
authors.initials: M
authors.lastname: Shimaoka
mesh_terms: D002465:Cell Movement / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D039001:Integrin alpha Chains / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019012:Integrin beta1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D011487:Protein Conformation; D015398:Signal Transduction / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D039001:Integrin alpha Chains; D019012:Integrin beta1