INVESTIGADORES
CROCI RUSSO Diego Omar
artículos
Título:
Nuclear factor (NF)-kB controls expression of the immunoregulatory glycan-binding protein galectin-1.
Autor/es:
TOSCANO MA; CAMPAGNA L; MOLINERO LL; CERLIANI JP; CROCI DO; ILARREGUI JM; FUERTES MB; NOJEK IM; FEDEDA JP; ZWIRNER NW; COSTAS MA; RABINOVICH GA
Revista:
MOLECULAR IMMUNOLOGY
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Lugar: Oxford; Año: 2011 vol. 48 p. 1940 - 1949
ISSN:
0161-5890
Resumen:
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-κB
activation. NF-κB-activating stimuli increased Gal-1 expression on T
cells, an effect which could be selectively prevented by inhibitors of
NF-κB signaling. Accordingly, transient transfection of the p65 subunit
of NF-κB was sufficient to induce high Gal-1 expression. Using in silico
studies and chromatin immunoprecipitation analysis we have identified a
functional NF-κB binding site within the first intron of the LGALS1
gene. In addition, our results show that exogenous Gal-1 can attenuate
NF-κB activation, as shown by inhibition of IκB-α degradation induced by
pro-inflammatory stimuli, higher cytoplasmic retention of p65, lower
NF-κB DNA binding activity and impaired transcriptional activation of
target genes. The present study suggest a novel regulatory loop by which
NF-κB induces expression of Gal-1, which in turn may lead to negative
control of NF-κB signaling.