Regulated expression and function of galectin-1 in inflammatory bowel diseases

PAPA GOBBI RODRIGO; ROCCA ANDRES; SAMBUELLI ALICIA; YANTORNO MARTÍN; TOSCANO MARTA; MUGLIA CECILIA; RABINOVICH GABRIEL; DOCENA GUILLERMO H.

Los Cocos

Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología; 2013

Inflammatory bowel diseases (IBD) are multifactorial disorders characterized by a chronic intestinal inflammation. Galectin-1, a ubiquitous endogenous lectin, has been implicated in several chronic inflammatory disorders. We aimed to analyze its role in the colonic mucosa of patients with Crohn?Ls disease (CD) and Ulcerative colitis (UC). Gal-1 expression was studied by qPCR, immunoblotting and histology in biopsies and resected tissues of patients with IBD (n=26) and control patients (n=20). Gal-1-specific binding ligands were also analyzed by flow cytometry in lamina propria and its physiologycal role in the induction of cell death was evaluated by flow cytometry. We found in 21 biopsies of CD and 22 biopsies of CU that expression of Gal-1 was increased in colonic inflamed areas (p<0.01), while protein expression was lower as compared to non-inflamed areas. Culture of control biopsies rendered a dose-response increase in the expression and secretion of Gal-1 when TNF-?¿ was added to the culture (1, 5 and 10 ng/mL) (p<0.05). Gal-1-specific binding sites were considerably reduced in isolated lamina propria CD4 or CD8 lymphocytes from inflamed areas (n=11), as compared to non-inflamed areas (n=10) or control samples (n=8) (p<0.05). A consistent lower binding of PNA was found in IBD samples, suggesting lower levels of asialo-core 1-O-glycans. When apoptosis was analyzed we found that 5 and 10 ng Gal-1 increased the frequency of annexin-1-positive cells (n=5) (17,94% with medium; 25,88% with 5 ng Gal-1 and 32,94 with 10 ng Gal-1. p<0,05) In conclusion, we found a differential expression of Gal-1 and Gal-1-specific glycosylated ligands in biological samples of IBD, which may influence the pathogenesis of these diseases. As Gal-1 exerts a pro-apoptotic effect in activated T lymphocytes, reduced expression of this protein in inflamed areas may have relevant implications in survival vs cell death of these cells, and in the persistency of inflammation in the affected colon