Espressione e ruolo funzionale di interleuchina-33 e del suo recettore, ST2, nelle malattie infiammatorie croniche intestinali

Pastorelli, Luca (2011) Espressione e ruolo funzionale di interleuchina-33 e del suo recettore, ST2, nelle malattie infiammatorie croniche intestinali, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Scienze chirurgiche: progetto n. 3 "Scienze medico-chirurgiche gastroenterologiche e dei trapianti", 23 Ciclo. DOI 10.6092/unibo/amsdottorato/4148.
Documenti full-text disponibili:
Documento PDF (Italiano) - Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Download (48MB) | Anteprima


IL-33 is a novel member of the IL-1 family and ligand for the IL-1 receptor-related protein, ST2. Recent evidence suggests that the IL-33/ST2 axis plays a critical role in several autoimmune and inflammatory disorders; however, its role in inflammatory bowel disease (IBD) has not been clearly defined. We characterized IL-33 and ST2 expression and modulation following conventional anti-TNF therapy in Crohn’s disease and ulcerative colitis (UC) patients, and investigated the role of IL-33 in SAMP1/YitFc (SAMP) mice, a mixed Th1/Th2 model of IBD. Our results showed a specific increase of mucosal IL-33 in active UC, localized primarily to intestinal epithelial cells (IEC) and colonic inflammatory infiltrates. Importantly, increased expression of full-length IL-33, representing the most bioactive form, was detected in UC epithelium, while elevated levels of cleaved IL-33 were present in IBD serum. ST2 isoforms were differentially modulated in UC epithelium and sST2, a soluble decoy receptor with anti-inflammatory properties, was also elevated in IBD serum. Infliximab (anti-TNF) treatment of UC decreased circulating IL-33 and increased sST2, while stimulation of HT-29 IEC confirmed IL-33 and sST2 regulation by TNF. Similarly, IL-33 significantly increased and correlated with disease severity, and potently induced IL-5, IL-6 and IL-17 from mucosal immune cells in SAMP mice. Taken together, the IL-33/ST2 system plays an important role in IBD and experimental colitis, is modulated by anti-TNF therapy, and may represent a specific biomarker for active UC.

Tipologia del documento
Tesi di dottorato
Pastorelli, Luca
Dottorato di ricerca
Scuola di dottorato
Scienze mediche e chirurgiche cliniche
Settore disciplinare
Settore concorsuale
Parole chiave
IL-33, ST2, sST2, ST2L, Inflammatory Bowel Disease, Ulcerative colitis, SAMP1/YitFc
Data di discussione
6 Settembre 2011

Altri metadati

Statistica sui download

Gestione del documento: Visualizza la tesi