The role of interleukin 17 in Crohn's disease-associated intestinal fibrosis

BIANCHERI P; PENDER S; AMMOSCATO F; GIUFFRIDA, P; SAMPIETRO G; ARDIZZONE S; GHANBARI A; CURCIARELLO R; PASSINI A; MONTELEONE G; CORAZZA GR; MACDONALD TT; DISABATTINO A

Fibrogenesis & Tissue Repair

BioMed Central

Año: 2013 vol. 6

1755-1536

Background Interleukin (IL)-17A and IL-17E (also known as IL-25) have been implic ated in fibrosis in various tissues. However, the role of these cytokines in the development of intestinal strictures in Crohn?s disease (CD) has not been explored. We investi gated the levels ofIL- 17A and IL-17E and their receptors in CD strictured and non-strictured gut, and the effects of IL-17A and IL-17E on CD myofibroblasts.. Results IL-17A was significantly overexpressed in strictured compared w ith non-strictured CD tissues, whereas no significant difference was found in the expre ssion of IL-17E or IL-17A and IL-17E receptors (IL-17RC and IL-17RB, respectively) in strictur ed and non-strictured CD areas. Strictured CD explants released significantly highe r amounts of IL-17A than non- strictured explants, whereas no difference was found as for IL-17E, IL-6, or tumor necrosis factor- α production. IL-17A, but not IL-17E, significantly inhibited myofibroblast migration, and also significantly upregulated matrix metalloproteinase (MMP )-3, MMP-12, tissue inhibitor of metalloproteinase-1 and collagen production by myofibroblast s from strictured CD tissues. Conclusions Our results suggest that IL-17A, but not IL-17E, is pro-fibrotic in C D. Further studies are needed to clarify whether the therapeutic blockade of IL-17A through the anti-IL-17A monoclonal antibody secukinumab is able to counteract the fibrogenic process in CD.