RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages

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.PMID:38343633 | PMC:PMC10857877 | DOI:10.1155/2024/2264799

Source: Journal of Immunology Research - February 12, 2024 Category: Allergy & Immunology Authors: Mar ía José Romero de Ávila Susana L ópez-López Aar ón García-Blázquez Almudena Ruiz-Garc ía Mar ía Julia González-Gómez Mar ía Luisa Nueda Victoriano Baladr ón Ignacio P érez-Roger Enric Poch Bego ña Ballester-Lurbe Jos é Javier García- Source Type: research