INVESTIGADORES
CURCIARELLO Renata
congresos y reuniones científicas
Título:
Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) Activation Increases the Production of Pro-Inflammatory Cytokines by Inflammatory Bowel Disease Mucosa
Autor/es:
FRANCESCA AMMOSCATO ; PAOLO BIANCHERI ; ANETA KUCIK; IONA M BELL; RENATA CURCIARELLO ; GEORGE BOUNDOUKI; LAURENS KRUIDENIER; THOMAS T, MACDONALD
Lugar:
Dublin
Reunión:
Congreso; European Mucosal Immunology Group- EMIG 2012; 2012
Resumen:
Background & Aim: Intestinal macrophages play an important role in the pathogenesis of inflammatory bowel disease (IBD). Inflamed IBD mucosa contains high numbers of CD33+CD68+ macrophages overexpressing Triggering receptor expressed on myeloid cells 1 (TREM-1). 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 an activating anti-TREM-1 monoclonal antibody, and the production of interleukin (IL)-1beta, IL-6 and IL-8 was determined by ELISA.
Results: The percentage of mucosal CD33+CD68+ macrophages was significantly higher both in Crohn's disease and ulcerative colitis in comparison to control subjects. Compared to control subjects, TREM-1 expression by mucosal macrophages was significantly higher both in ulcerative colitis and in Crohn's disease compared to control subjects. TREM-1 activation significantly increased IL-1beta, IL-6 and IL-8 production by IBD biopsies cultured ex vivo.
Conclusions: TREM-1 is overexpressed on macrophages in IBD mucosa, and its activation amplifies the production of pro-inflammatory cytokines. Further studies using chromatin immunoprecipitation assays are under way in order to establish whether TREM-1 overexpression in IBD may derive from epigenetic changes.