title: IL-17A increases ADP-induced platelet aggregation.
abstract: The increased risk of thromboembolism and higher incidence of cardiovascular disorders are among the most common causes of morbidity in patients suffering from autoimmune diseases. In this study we tested the hypothesis that IL-17A, a key pro-inflammatory cytokine involved in the development of autoimmune diseases, exerts pro-aggregant effects on both human and mouse platelets. Human or murine platelets were incubated with IL-17A for 2 min at 37°C prior the addition of the stimuli. Aggregation was monitored in a light transmission aggregometer measuring changes in turbidity with continuous observation over a 5-min interval after the addition of the stimuli. IL-17RA, CD42b and CD62P expression as well as fibrinogen bindings were measured by FACS while Erk-2 phosphorylation was analyzed by western blot using phospho-specific antibodies. Pre-incubation with IL-17A increased ADP-, but not collagen-induced platelet aggregation and accelerated CD62P expression and exposure of fibrinogen binding sites. These effects were associated with a faster kinetic of ADP-induced Erk-2 phosphorylation and were lost in platelets deficient in the IL-17 receptor. Together these results unveil a novel aspect of the inflammatory nature of IL-17A suggesting, at the same time, that therapeutic strategies targeting this cytokine might provide further benefit for the treatment of autoimmune diseases by reducing the risk of cardiovascular-related pathologies.
authors.affiliation: William Harvey Research Institute, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, Charterhouse Square, London, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Maione
authors.forename: Carla
authors.initials: C
authors.lastname: Cicala
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Liverani
authors.forename: Nicola
authors.initials: N
authors.lastname: Mascolo
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
authors.forename: Fulvio
authors.initials: F
authors.lastname: D'Acquisto
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D053722:Receptors, Interleukin-17 / Q000235:genetics; D013923:Thromboembolism / Q000209:etiology / Q000235:genetics / Q000503:physiopathology
chemical_list: C508717:IL17A protein, human; C491673:Il17ra protein, mouse; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D000244:Adenosine Diphosphate