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P025 Transcriptional and molecular pathways activated in mesenteric adipose tissue and intestinal mucosa of Crohn's disease patients

Coope A.1, Pascoal L.B.1, Silva F.A.R.1, Botezelli J.D.1, Ayrizono M.L.S.1, Milanski M.2, Camargo M.G.1, Planell N.3, Portovedo M.2, Dias C.B.1, Fagundes J.J.1, Leal R.F.*1

1University of Campinas, Department of Surgery, IBD Research Laboratory, Campinas, Brazil 2University of Campinas, Cell Signaling Laboratory, Department of Internal Medicine, Campinas, Brazil 3IDIBAPS, CIBERehd, Bioinformatics Platform, Barcelona, Spain

Background

Crohn's disease (CD) is a chronic inflammatory disorder, characterized by cytokine imbalance and transcription signaling pathways activation. In addition, increase of mesenteric adipose tissue (MAT) near the affected intestinal area is a hallmark of CD, and its role has been studied. Therefore, we evaluated the transcription signaling pathways and cytokines expression in intestinal mucosa and MAT of active CD patients.

Methods

Ten patients with ileocecal CD and eight with non-inflammatory diseases were studied. Histological analysis was performed by Haematoxylin-eosin staining (H&E). The biopsies of intestinal mucosa and MAT were snap-frozen and proteins expression were determined by immunoblotting. RNA levels were measured by qPCR.

Results

H&E showed crypt distortion, ulcers and inflammatory infiltrate in intestinal mucosa and reduced adipocyte size in MAT. The p-IkB/IkB ratio and TNFα level were significantly higher in intestinal mucosa of CD when compared to controls. However, STAT-1 expression was similar between intestinal mucosa of CD and controls. Considering the MAT, the p-IkB/IkB ratio was significantly lower and anti-inflammatory cytokine IL-10 was significantly higher in CD when compared to controls. Additionally, no differences was observed in TNFα, IL6, IL8, IL23, IL10 and STAT1 gene expression in MAT of CD patients compared to controls. Finally, the protein content of p-STAT1 was higher in MAT of CD compared to controls.

Conclusion

These findings reinforce the predominance of the pro-inflammatory NF-kB pathway in CD intestinal mucosa. For the first time, we showed the activation of STAT1 pathway in MAT of CD patients, which may help to understand the physiopathology of this immune mediated disease.