Beneficial effects of treatment with transglutaminase inhibitor cystamine on the severity of inflammation in a rat model of inflammatory bowel disease

Luca Elli, Michele M. Ciulla, Giuseppe Busca, Leda Roncoroni, Claudio Maioli, Stefano Ferrero, Maria Teresa Bardella, Antonella Bonura, Roberta Paliotti, Claudia Terrani, Paola Braidotti

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammatory bowel disease (IBD) represents a socially and clinically relevant disorder, characterized by intestinal chronic inflammation. Cystamine (CysN) is a multipotent molecule with healthy effects and, moreover, it is an inhibitor of transglutaminases (TGs), including the TG type 2 (TG2), an enzyme with pleiotropic functions, involved in different pathways of inflammation and central in the pathogenesis of some human disorders as the IBD. Our aim was to evaluate the effect of CysN in an IBD rat model. A total of 30 rats were divided into 4 groups: controls without treatment (CTR; n7); receiving the 2,4,6-trinitrobenzene sulfonic acid enema (TNBS group; n8); treated with TNBS enema plus oral CysN (TNBS-CysN group; n8); treated with CysN (CysN group; n7). After killing, bowel inflammation was evaluated applying specific scores. TG activity, TG2 and isopeptide bond immunohistochemical expression, and tumor necrosis factor-α (TNF-α) were evaluated in the colonic tissue, such as interleukin-6 (IL-6) serological levels (ELISA). TG2 was also evaluated on the luminal side of the colon by immunoautoradiography. Colonic samples from IBD patients were compared with animal results. TNBS-CysN group developed a less severe colitis compared with the TNBS group (macroscopic score 0.43±0.78 vs 3.28±0.95, microscopic score 6.62±12.01 vs 19.25±6.04, P

Original languageEnglish
Pages (from-to)452-461
Number of pages10
JournalLaboratory Investigation
Volume91
Issue number3
DOIs
Publication statusPublished - Mar 2011

Keywords

  • colitis
  • cystamine
  • inflammatory bowel disease
  • transglutaminase type 2

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Molecular Biology

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