Abstract

Inflammatory bowel disease (Crohn's disease (CD) and ulcerative colitis (UC)) is a multifactorial disease resulting from immune dysregulation in the gut. The underlying colitis is characterized by high levels of inflammatory cytokines, including TNF alpha. Biological intervention for IBD patients using anti-TNF alpha antibodies is often an effective therapeutic solution. However, TNF alpha neutralization fails to induce remission in a subgroup of IBD patients, primarily in UC patients. There is a dearth of suitable animal models representing TNF alpha non-responders. Here we have combined one of the best UC models currently available, namely Winnie and the TNF alpha KO mouse to generate a TNF alpha-deficient Winnie to study early onset colitis. The induced TNF alpha deficiency with underlying colitis does not influence general health (viability and body weight) or clinical parameters (colon weight, colon length and histological colitis) when compared with the Winnie genotype alone. The molecular characterization resulted in identification of Il1 beta as the major elevated cytokine during early phases of colitis. Further, in vitro functional assay using bone marrow-derived dendritic cells confirmed IL-1 beta as the major cytokine released in the absence of TNF alpha. This study has generated a successful model of colitis that remains TNF alpha non-responsive and has demonstrated that IL-1 beta expression is a major pathway for theprogression of colitis in this system. These data also suggest that IL-1 beta can be a potential target for clinical intervention of UC patients who fail to respond to TNF alpha neutralization.

Autore Pugliese

• Santino Angelo

Tutti gli autori

• De Santis S.; Kunde D.; Galleggiante V.; Liso M.; Scandiffio L.; Serino G.; Pinto A.; Campiglia P.; Sorrentino R.; Cavalcanti E.; Santino A.; Caruso M. L.; Eri R.; Chieppa M.

Titolo volume/Rivista

Cell death and disease

Anno di pubblicazione

2017

ISSN

2041-4889

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

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Numero di citazioni Scopus

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Ultimo Aggiornamento Citazioni

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Settori ERC

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Codici ASJC

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