Activation of triggering receptor expressed on myeloid cells 1 (TREM-1) activation increases the production of pro-inflammatory cytokines by inflammatory bowel disease mucosa

FRANCESCA AMMOSCATO; PAOLO BIANCHERI; ANETA KUCIK; IONA M BELL; RENATA CURCIARELLO; GEORGE BOUNDOUKI; LAURENS KRUIDENIER; THOMAS T, MACDONALD

Amsterdam

Congreso; 20th United European Gastroenterology Week-UEGW 2012; 2012

Background & Aim: Intestinal macrophages play a central role in the pathogenesis of inflammatory bowel disease (IBD). The phenotype of mucosal macrophages changes dramatically at the site of inflammation, where high numbers of CD33+CD68+ macrophages overexpress TLRs, CD14 and triggering receptor expressed on myeloid cells 1 (TREM-1). TREM-1 is expressed on the surface of neutrophils and macrophages and contributes to the amplification of inflammatory responses by enhancing degranulation and secretion of pro-inflammatory mediators. After comparing the percentage of TREM-1-expressing macrophages in IBD versus control mucosa, we explored the ex vivo effects of a TREM-1 activating antibody on the intestinal immune response in IBD. Material & Methods: Lamina propria mononuclear cells (LPMCs) were isolated from the inflamed colon of 11 IBD patients (5 ulcerative colitis and 6 Crohn?s disease), and from normal colon of 8 control subjects, and the expression of CD68, CD33 and TREM-1 was analysed by flow cytometry. IBD biopsies from inflamed mucosa were cultured ex vivo with or without a TREM-1 agonist, and the production of pro-inflammatory cytokines, namely interleukin (IL)-1, IL-6 and IL-8, was determined by ELISA. Results: The percentage of mucosal CD33+CD68+ macrophages was significantly (p