title: Sulfonamide inhibitors of α2β1 integrin reveal the essential role of collagen receptors in in vivo models of inflammation.
abstract: Small molecule inhibitors of α2β1 integrin, a major cellular collagen receptor, have been reported to inhibit platelet function, kidney injury, and angiogenesis. Since α2β1 integrin is abundantly expressed on various inflammation-associated cells, we tested whether recently developed α2β1 blocking sulfonamides have anti-inflammatory properties. Integrin α2β1 inhibitors were shown to reduce the signs of inflammation in arachidonic acid-induced ear edema, PAF stimulated air pouch, ovalbumin-induced skin hypersensitivity, adjuvant arthritis, and collagen-induced arthritis. Thus, these sulfonamides are potential drugs for acute and allergic inflammation, hypersensitivity, and arthritis. One sulfonamide with potent anti-inflammatory activity has previously been reported to be selective for activated integrins, but not to inhibit platelet function. Thus, the experiments also revealed fundamental differences in the action of nonactivated and activated α2β1 integrins in inflammation when compared to thrombosis.
authors.affiliation: Department of Biochemistry, University of Turku 20014, Turku, Finland ; Biotie Therapies Corp Turku, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Nissinen
authors.affiliation: Biotie Therapies Corp Turku, Finland.
authors.forename: Marika
authors.initials: M
authors.lastname: Ojala
authors.affiliation: BioTie Therapies GmbH Radebeul, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Langen
authors.affiliation: BioTie Therapies GmbH Radebeul, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Dost
authors.affiliation: Biotie Therapies Corp Turku, Finland.
authors.forename: Marjo
authors.initials: M
authors.lastname: Pihlavisto
authors.affiliation: Department of Biochemistry, University of Turku 20014, Turku, Finland.
authors.forename: Jarmo
authors.initials: J
authors.lastname: Käpylä
authors.affiliation: Department of Biochemistry, University of Turku 20014, Turku, Finland ; Biotie Therapies Corp Turku, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Marjamäki
authors.affiliation: Department of Biochemistry, University of Turku 20014, Turku, Finland.
authors.forename: Jyrki
authors.initials: J
authors.lastname: Heino
keywords: Cell adhesion; collagen; inflammation; integrin; sulfonamide