Nuclear factor (NF) -kappa B controls expression of the immunoregulatory glycan-binding protein galectin-1

TOSCANO MA*; CAMPAGNA L; MOLINERO L; CERLIANI JP; CROCI DO; ILARREGUI JM; FUERTES MB; NOJEK IM; FEDEDA JP; ZWIRNER NW; COSTAS MA; RABINOVICH GA*; * AUTOR DE CORRESPONDENCIA

MOLECULAR IMMUNOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2011 vol. 48 p. 1940 - 1949

0161-5890

The inflammatory response is a self-limiting process which involves the sequential activation of signaling pathways leading to the production of both pro- and anti-inflammatory mediators. Galectin-1 (Gal-1), an endogenous lectin found in peripheral lymphoid organs and inflammatory sites, elicits a broad spectrum of biological functions predominantly by acting as a potent anti-inflammatory factor and as a suppressive agent for T-cell responses. However, the molecular pathways underlying Gal-1 expression and function remain poorly understood. Here we identified a regulatory loop linking Gal-1 expression and function to NF-kappaB activation. NF-kappaB-activating stimuli increased Gal-1 expression on T cells, an effect which could be selectively prevented by inhibitors of NF-kappaB signaling. Accordingly, transient transfection of the p65 subunit of NF-kappaB was sufficient to induce high Gal-1 expression. Using in silico studies and chromatin immunoprecipitation analysis we have identified a functional NF-kappaB binding site within the first intron of the LGALS1 gene. In addition, our results show that exogenous Gal-1 can attenuate NF-kappaB  activation, as shown by inhibition of IkappaB-alpha degradation induced by pro-inflammatory stimuli, higher cytoplasmic retention of p65, lower NF-kappaB DNA binding activity and impaired transcriptional activation of target genes. The present study suggest a novel regulatory loop by which NF-kappaB induces expression of Gal-1, which in turn may lead to negative control of NF-B signaling.