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

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 NE-kappa B activation. NE-kappa B-activating stimuli increased Gal-1 expression on T cells, an effect which could be selectively prevented by inhibitors of NE-kappa B signaling. Accordingly, transient transfection of the p65 subunit of NE-kappa B was sufficient to induce high Gal-1 expression. Using in silico studies and chromatin immunoprecipitation analysis we have identified a functional NE-kappa B binding site within the first intron of the LGALS1 gene. In addition, our results show that exogenous Gal-1 can attenuate NE-kappa B activation, as shown by inhibition of I kappa B-alpha degradation induced by pro-inflammatory stimuli, higher cytoplasmic retention of p65, lower NE-kappa B DNA binding activity and impaired transcriptional activation of target genes. The present study suggest a novel regulatory loop by which NE-kappa B induces expression of Gal-1, which in turn may lead to negative control of NE-kappa B signaling. (C) 2011 Elsevier Ltd. All rights reserved.