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 b...
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todo:paper_01615890_v48_n15-16_p1940_Toscano2023-10-03T15:01:21Z Nuclear factor (NF)-κB controls expression of the immunoregulatory glycan-binding protein galectin-1 Toscano, M.A. Campagna, L. Molinero, L.L. Cerliani, J.P. Croci, D.O. Ilarregui, J.M. Fuertes, M.B. Nojek, I.M. Fededa, J.P. Zwirner, N.W. Costas, M.A. Rabinovich, G.A. Galectin-1 Inflammation NF-κB T cells galectin 1 glycan I kappa B alpha immunoglobulin enhancer binding protein protein subunit synaptotagmin I tacrolimus tumor necrosis factor alpha article binding site cell differentiation chromatin immunoprecipitation chromosome 22 controlled study cytoplasm DNA binding down regulation gene targeting genetic transfection human human cell immunoregulation inflammation inhibition kinetics intron peripheral blood mononuclear cell priority journal protein analysis protein degradation protein expression protein function protein protein interaction signal transduction Th1 cell Th2 cell transcription initiation transcription initiation site Western blotting Binding Sites Blotting, Western Cells, Cultured Chromatin Immunoprecipitation Electrophoretic Mobility Shift Assay Feedback, Physiological Galectin 1 Gene Expression Gene Expression Regulation Humans Microscopy, Confocal NF-kappa B Reverse Transcriptase Polymerase Chain Reaction Signal Transduction T-Lymphocytes Transfection 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. © 2011 Elsevier Ltd. Fil:Toscano, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Molinero, L.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Croci, D.O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ilarregui, J.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fuertes, M.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Nojek, I.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fededa, J.P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Costas, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_01615890_v48_n15-16_p1940_Toscano |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Galectin-1 Inflammation NF-κB T cells galectin 1 glycan I kappa B alpha immunoglobulin enhancer binding protein protein subunit synaptotagmin I tacrolimus tumor necrosis factor alpha article binding site cell differentiation chromatin immunoprecipitation chromosome 22 controlled study cytoplasm DNA binding down regulation gene targeting genetic transfection human human cell immunoregulation inflammation inhibition kinetics intron peripheral blood mononuclear cell priority journal protein analysis protein degradation protein expression protein function protein protein interaction signal transduction Th1 cell Th2 cell transcription initiation transcription initiation site Western blotting Binding Sites Blotting, Western Cells, Cultured Chromatin Immunoprecipitation Electrophoretic Mobility Shift Assay Feedback, Physiological Galectin 1 Gene Expression Gene Expression Regulation Humans Microscopy, Confocal NF-kappa B Reverse Transcriptase Polymerase Chain Reaction Signal Transduction T-Lymphocytes Transfection |
| spellingShingle |
Galectin-1 Inflammation NF-κB T cells galectin 1 glycan I kappa B alpha immunoglobulin enhancer binding protein protein subunit synaptotagmin I tacrolimus tumor necrosis factor alpha article binding site cell differentiation chromatin immunoprecipitation chromosome 22 controlled study cytoplasm DNA binding down regulation gene targeting genetic transfection human human cell immunoregulation inflammation inhibition kinetics intron peripheral blood mononuclear cell priority journal protein analysis protein degradation protein expression protein function protein protein interaction signal transduction Th1 cell Th2 cell transcription initiation transcription initiation site Western blotting Binding Sites Blotting, Western Cells, Cultured Chromatin Immunoprecipitation Electrophoretic Mobility Shift Assay Feedback, Physiological Galectin 1 Gene Expression Gene Expression Regulation Humans Microscopy, Confocal NF-kappa B Reverse Transcriptase Polymerase Chain Reaction Signal Transduction T-Lymphocytes Transfection Toscano, M.A. Campagna, L. Molinero, L.L. Cerliani, J.P. Croci, D.O. Ilarregui, J.M. Fuertes, M.B. Nojek, I.M. Fededa, J.P. Zwirner, N.W. Costas, M.A. Rabinovich, G.A. Nuclear factor (NF)-κB controls expression of the immunoregulatory glycan-binding protein galectin-1 |
| topic_facet |
Galectin-1 Inflammation NF-κB T cells galectin 1 glycan I kappa B alpha immunoglobulin enhancer binding protein protein subunit synaptotagmin I tacrolimus tumor necrosis factor alpha article binding site cell differentiation chromatin immunoprecipitation chromosome 22 controlled study cytoplasm DNA binding down regulation gene targeting genetic transfection human human cell immunoregulation inflammation inhibition kinetics intron peripheral blood mononuclear cell priority journal protein analysis protein degradation protein expression protein function protein protein interaction signal transduction Th1 cell Th2 cell transcription initiation transcription initiation site Western blotting Binding Sites Blotting, Western Cells, Cultured Chromatin Immunoprecipitation Electrophoretic Mobility Shift Assay Feedback, Physiological Galectin 1 Gene Expression Gene Expression Regulation Humans Microscopy, Confocal NF-kappa B Reverse Transcriptase Polymerase Chain Reaction Signal Transduction T-Lymphocytes Transfection |
| description |
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. © 2011 Elsevier Ltd. |
| format |
JOUR |
| author |
Toscano, M.A. Campagna, L. Molinero, L.L. Cerliani, J.P. Croci, D.O. Ilarregui, J.M. Fuertes, M.B. Nojek, I.M. Fededa, J.P. Zwirner, N.W. Costas, M.A. Rabinovich, G.A. |
| author_facet |
Toscano, M.A. Campagna, L. Molinero, L.L. Cerliani, J.P. Croci, D.O. Ilarregui, J.M. Fuertes, M.B. Nojek, I.M. Fededa, J.P. Zwirner, N.W. Costas, M.A. Rabinovich, G.A. |
| author_sort |
Toscano, M.A. |
| title |
Nuclear factor (NF)-κB controls expression of the immunoregulatory glycan-binding protein galectin-1 |
| title_short |
Nuclear factor (NF)-κB controls expression of the immunoregulatory glycan-binding protein galectin-1 |
| title_full |
Nuclear factor (NF)-κB controls expression of the immunoregulatory glycan-binding protein galectin-1 |
| title_fullStr |
Nuclear factor (NF)-κB controls expression of the immunoregulatory glycan-binding protein galectin-1 |
| title_full_unstemmed |
Nuclear factor (NF)-κB controls expression of the immunoregulatory glycan-binding protein galectin-1 |
| title_sort |
nuclear factor (nf)-κb controls expression of the immunoregulatory glycan-binding protein galectin-1 |
| url |
http://hdl.handle.net/20.500.12110/paper_01615890_v48_n15-16_p1940_Toscano |
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