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

TOSCANO, MARTA ALICIA; CAMPAGNA, LEONARDO; MOLINERO, LUCIANA LORENA; CERLIANI, JUAN PABLO; CROCI RUSSO, DIEGO; ILARREGUI, JUAN MARTÍN; FUERTES, MERCEDES BEATRIZ; NOJEK, IGNACIO M.; FEDEDA, JUAN PABLO; ZWIRNER, NORBERTO WALTER; COSTAS, MÓNICA ALEJANDRA; RABINOVICH, GABRIEL ADRIÁN

MOLECULAR IMMUNOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

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