2026-06-08T01:17:53Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1177712025-03-18T12:28:00Zcom_20.500.14352_14col_20.500.14352_15

NF-κB-Inducing Kinase Is Essential for Effective c-Rel Transactivation and Binding to the Il12b Promoter in Macrophages Cuesta Rubio, Natalia Staniszewska, Anna D. Moreno, Cristóbal Punzón, Carmen Fresno, Manuel 576 577.2 NIK c-Rel IL-12 macrophages LPS Biología molecular (Biología) Bioquímica (Biología) Biología celular (Biología) 2403 Bioquímica 2407 Biología Celular 2415 Biología Molecular This study investigates the role of NIK in activating specific inflammatory genes in macrophages, focusing on the effect of a mutation in NIK found in alymphoplasia (aly/aly) mice. Mouse peritoneal macrophages from aly/aly mice showed a severe defect in the production of some pro-inflammatory cytokines, such as IL-12. This effect seemed to take place at the transcriptional level, as shown by the reduced transcription of Il12b and Il12a in aly/aly macrophages after exposure to the TLR4 agonist LPS. Immunoprecipitation studies showed that the binding of NIK to c-Rel was not efficient in RAW 264.7 cells over-expressing the aly/aly mutation. In addition, the shuttling of c-Rel to the nucleus was shown to be impaired in aly/aly macrophages in response to LPS. When looking more specifically at the regulation of the Il12b promoter, we found that c-Rel bound to the NF-kB consensus sequence in macrophages from WT mice 1 hr. after LPS challenge, whereas in aly/aly macrophages, the transcription factor bound to the promoter was p65. These findings indicate that NIK is essential for efficient c-Rel activation and proper inflammatory responses. NIK dysfunction could lead to weakened immune responses, and targeting this pathway may help in developing therapies for immune-related conditions. Ministerio de Ciencia e Innovación (España) Comunidad Autónoma de Madrid Instituto de Salud Carlos III Depto. de Biología Celular Fac. de Medicina TRUE pub 2025-02-04T07:51:25Z 2025-02-04T07:51:25Z 2025-01-03 journal article VoR https://hdl.handle.net/20.500.14352/117771 2079-7737 10.3390/biology14010033 eng info:eu-repo/grantAgreement/MinisteriodeCienciaeInnovación/MECI-SAF2007-61716 info:eu-repo/grantAgreement/MinisteriodeCienciaeInnovación/MECI-SAF2010-18733 info:eu-repo/grantAgreement/ComunidaddeMadrid/S2010/BMD 2332 info:eu-repo/grantAgreement/Institutodesaludcarlosiii/redRECAVA/RD06/0014/1013 Cuesta N, Staniszewska AD, Moreno C, Punzón C, Fresno M. NF-κB-Inducing Kinase Is Essential for Effective c-Rel Transactivation and Binding to the Il12b Promoter in Macrophages. Biology (Basel). 2025 Jan 3;14(1):33. Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ open access application/pdf MDPI