title: Nuclear factor (NF)-κB controls expression of the immunoregulatory glycan-binding protein galectin-1.
abstract: 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.
authors.affiliation: Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires, Argentina. martalitos@yahoo.com.ar
authors.forename: Marta A
authors.initials: MA
authors.lastname: Toscano
authors.forename: Leonardo
authors.initials: L
authors.lastname: Campagna
authors.forename: Luciana L
authors.initials: LL
authors.lastname: Molinero
authors.forename: Juan P
authors.initials: JP
authors.lastname: Cerliani
authors.forename: Diego O
authors.initials: DO
authors.lastname: Croci
authors.forename: Juan M
authors.initials: JM
authors.lastname: Ilarregui
authors.forename: Mercedes B
authors.initials: MB
authors.lastname: Fuertes
authors.forename: Ignacio M
authors.initials: IM
authors.lastname: Nojek
authors.forename: Juan P
authors.initials: JP
authors.lastname: Fededa
authors.forename: Norberto W
authors.initials: NW
authors.lastname: Zwirner
authors.forename: Mónica A
authors.initials: MA
authors.lastname: Costas
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Rabinovich
mesh_terms: D001665:Binding Sites; D015153:Blotting, Western; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D025461:Feedback, Physiological / Q000502:physiology; D037483:Galectin 1 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014162:Transfection
chemical_list: D037483:Galectin 1; C445499:LGALS1 protein, human; D016328:NF-kappa B