A1 Refereed original research article in a scientific journal

Sulfonamide inhibitors of α2β1 integrin reveal the essential role of collagen receptors in in vivo models of inflammation.




AuthorsNissinen L, Ojala M, Langen B, Dost R, Pihlavisto M, Käpylä J, Marjamäki A, Heino J.

Publication year2015

JournalPharmacology Research and Perspectives

Journal acronymPharmacol Res Perspect

Article numbere00146

Volume3

Issue3

Number of pages11

ISSN2052-1707

DOIhttps://doi.org/10.1002/prp2.146


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.




Last updated on 2024-26-11 at 20:17