RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages
Macrophage activation is a complex process with multiple control elements that ensures an adequate response to the aggressor pathogens and, on the other hand, avoids an excess of inflammatory activity that could cause tissue damage. In this study, we have identified RND3, a small GTP-binding protein...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2024/2264799 |
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| author | María José Romero de Ávila Susana López-López Aarón García-Blázquez Almudena Ruiz-García María Julia González-Gómez María Luisa Nueda Victoriano Baladrón Ignacio Pérez-Roger Enric Poch Begoña Ballester-Lurbe José Javier García-Ramírez Eva M. Monsalve María José M. Díaz-Guerra |
| author_facet | María José Romero de Ávila Susana López-López Aarón García-Blázquez Almudena Ruiz-García María Julia González-Gómez María Luisa Nueda Victoriano Baladrón Ignacio Pérez-Roger Enric Poch Begoña Ballester-Lurbe José Javier García-Ramírez Eva M. Monsalve María José M. Díaz-Guerra |
| author_sort | María José Romero de Ávila |
| collection | DOAJ |
| description | Macrophage activation is a complex process with multiple control elements that ensures an adequate response to the aggressor pathogens and, on the other hand, avoids an excess of inflammatory activity that could cause tissue damage. In this study, we have identified RND3, a small GTP-binding protein, as a new element in the complex signaling process that leads to macrophage activation. We show that RND3 expression is transiently induced in macrophages activated through Toll receptors and potentiated by IFN-γ. We also demonstrate that RND3 increases NOTCH signaling in macrophages by favoring NOTCH1 expression and its nuclear activity; however, Rnd3 expression seems to be inhibited by NOTCH signaling, setting up a negative regulatory feedback loop. Moreover, increased RND3 protein levels seem to potentiate NFκB and STAT1 transcriptional activity resulting in increased expression of proinflammatory genes, such as Tnf-α, Irf-1, or Cxcl-10. Altogether, our results indicate that RND3 seems to be a new regulatory element which could control the activation of macrophages, able to fine tune the inflammatory response through NOTCH. |
| format | Article |
| id | doaj-art-dd2c93a234c849d8a88d5e6ba21286a8 |
| institution | OA Journals |
| issn | 2314-7156 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-dd2c93a234c849d8a88d5e6ba21286a82025-08-20T02:21:33ZengWileyJournal of Immunology Research2314-71562024-01-01202410.1155/2024/2264799RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated MacrophagesMaría José Romero de Ávila0Susana López-López1Aarón García-Blázquez2Almudena Ruiz-García3María Julia González-Gómez4María Luisa Nueda5Victoriano Baladrón6Ignacio Pérez-Roger7Enric Poch8Begoña Ballester-Lurbe9José Javier García-Ramírez10Eva M. Monsalve11María José M. Díaz-Guerra12Medical SchoolMedical SchoolMedical SchoolBiochemistry and Molecular Biology BranchMedical SchoolBiochemistry and Molecular Biology BranchMedical SchoolDepartment of Biomedical Sciences School of Health SciencesDepartment of Biomedical Sciences School of Health SciencesDepartment of Biomedical Sciences School of Health SciencesMedical SchoolMedical SchoolMedical SchoolMacrophage activation is a complex process with multiple control elements that ensures an adequate response to the aggressor pathogens and, on the other hand, avoids an excess of inflammatory activity that could cause tissue damage. In this study, we have identified RND3, a small GTP-binding protein, as a new element in the complex signaling process that leads to macrophage activation. We show that RND3 expression is transiently induced in macrophages activated through Toll receptors and potentiated by IFN-γ. We also demonstrate that RND3 increases NOTCH signaling in macrophages by favoring NOTCH1 expression and its nuclear activity; however, Rnd3 expression seems to be inhibited by NOTCH signaling, setting up a negative regulatory feedback loop. Moreover, increased RND3 protein levels seem to potentiate NFκB and STAT1 transcriptional activity resulting in increased expression of proinflammatory genes, such as Tnf-α, Irf-1, or Cxcl-10. Altogether, our results indicate that RND3 seems to be a new regulatory element which could control the activation of macrophages, able to fine tune the inflammatory response through NOTCH.http://dx.doi.org/10.1155/2024/2264799 |
| spellingShingle | María José Romero de Ávila Susana López-López Aarón García-Blázquez Almudena Ruiz-García María Julia González-Gómez María Luisa Nueda Victoriano Baladrón Ignacio Pérez-Roger Enric Poch Begoña Ballester-Lurbe José Javier García-Ramírez Eva M. Monsalve María José M. Díaz-Guerra RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages Journal of Immunology Research |
| title | RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages |
| title_full | RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages |
| title_fullStr | RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages |
| title_full_unstemmed | RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages |
| title_short | RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages |
| title_sort | rnd3 potentiates proinflammatory activation through notch signaling in activated macrophages |
| url | http://dx.doi.org/10.1155/2024/2264799 |
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