2026-06-07T13:54:33Zhttps://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
Docta Complutense author Cuesta Rubio, Natalia author Staniszewska, Anna D. author Moreno, Cristóbal author Punzón, Carmen author Fresno, Manuel 2025-02-04T07:51:25Z 2025-02-04T07:51:25Z 2025-01-03 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. 2079-7737 10.3390/biology14010033 https://hdl.handle.net/20.500.14352/117771 https://doi.org/10.3390/biology14010033 https://www.mdpi.com/2079-7737/14/1/33 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. eng Attribution 4.0 International NF-κB-Inducing Kinase Is Essential for Effective c-Rel Transactivation and Binding to the Il12b Promoter in Macrophages journal article 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URL https://docta.ucm.es/bitstreams/a29d58fd-b20a-4424-8947-0f7c89110db6/download File MD5 3dcb0629a979a675de69fdcd9d8d82cb 1876543 application/pdf NF-κB-Inducing Kinase Is Essential for Effective c-Rel Transactivation.pdf URL https://docta.ucm.es/bitstreams/87888ae2-ce67-485b-b326-6ff19fe981ab/download File MD5 b950777294f9b2f7bba922c80806215f 63616 text/plain NF-κB-Inducing Kinase Is Essential for Effective c-Rel Transactivation.pdf.txt