NFκB induces overexpression of bovine FcRn
| Autor: | Judit Cervenak, Balázs Mayer, Zita Schneider, Márton Doleschall, Lennart Hammarström, Wolfgang Oster, Yaofeng Zhao, Imre Kacskovics, Balázs Bender, Zoltán Doleschall, Zsuzsanna Bősze |
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| Rok vydání: | 2013 |
| Předmět: |
Lipopolysaccharides
Genetically modified mouse Transgene Immunology Antigen presentation Gene Expression Receptors Fc Biology Cell Line Animals Genetically Modified Mice Neonatal Fc receptor Adjuvants Immunologic Antigen Report Animals Humans Immunology and Allergy Northern blot Promoter Regions Genetic Antigen-presenting cell Binding Sites Antigen processing Histocompatibility Antigens Class I NF-kappa B Endothelial Cells Molecular biology Cattle Spleen |
| Zdroj: | mAbs. 5:860-871 |
| ISSN: | 1942-0870 1942-0862 |
| DOI: | 10.4161/mabs.26507 |
| Popis: | Among the many functions of the neonatal Fc receptor (FcRn) for IgG, it binds to IgG-opsonized antigen complexes and propagates their traffic into lysosomes where antigen processing occurs. We previously reported that transgenic (Tg) mice and rabbits that carry multiple copies and overexpress FcRn have augmented humoral immune responses. Nuclear factor-kappa B (NFκB) is a critical molecule in the signaling cascade in the immune response. NFκB induces human FcRn expression and our previous in silico analysis suggested NFκB binding sites in the promoter region of the bovine (b) FcRn α-chain gene (FCGRT). Here, we report the identification of three NFκB transcription binding sites in the promoter region of this gene using luciferase reporter gene technology, electromobility shift assay and supershift analysis. Stimulation of primary bovine endothelial cells with the Toll-like receptor-4 ligand lipopolysaccharide (LPS), which mediates its effect via NFκB, resulted in rapid upregulation of the bFcRn expression and a control gene, bovine E-selectin. This rapid bFcRn gene induction was also observed in the spleen of bFcRn Tg mice treated with intraperitoneally injected LPS, analyzed by northern blot analysis. Finally, NFκB-mediated bFcRn upregulation was confirmed at the protein level in macrophages isolated from the bFcRn Tg mice using flow cytometry with a newly developed FcRn specific monoclonal antibody that does not cross-react with the mouse FcRn. We conclude that NFκB regulates bFcRn expression and thus optimizes its functions, e.g., in the professional antigen presenting cells, and contributes to the much augmented humoral immune response in the bFcRn Tg mice. |
| Databáze: | OpenAIRE |
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