Medical School, Biomedicine Institute (IB-UCLM)/Biomedicine Unit, University of Castilla-La Mancha/CSIC, C/Almansa 14, 02008, Albacete, Spain.
Research Unit, University Hospital Complex of Albacete, C/Laurel s/n, 02008, Albacete, Spain.
J Immunol Res. 2024 Feb 2;2024:2264799. doi: 10.1155/2024/2264799. eCollection 2024.
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-. 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 NFB and STAT1 transcriptional activity resulting in increased expression of proinflammatory genes, such as -, , or . 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.
巨噬细胞的激活是一个复杂的过程，其中涉及多个控制元件，以确保对病原体的侵袭做出充分的反应，同时避免过度的炎症活动造成组织损伤。在这项研究中，我们发现 RND3 是一个新的小 GTP 结合蛋白，它是导致巨噬细胞激活的复杂信号转导过程中的一个新元件。我们表明，通过 Toll 受体激活的巨噬细胞中 RND3 的表达是短暂诱导的，并且可以被 IFN-增强。我们还证明，RND3 通过促进 NOTCH1 的表达及其核活性来增加巨噬细胞中的 NOTCH 信号；然而，Rnd3 的表达似乎受到 NOTCH 信号的抑制，形成负反馈调节回路。此外，RND3 蛋白水平的增加似乎增强了 NF-B 和 STAT1 的转录活性，导致促炎基因如 、 或 的表达增加。总的来说，我们的结果表明，RND3 似乎是一个新的调节元件，能够控制巨噬细胞的激活，通过 NOTCH 来精细调节炎症反应。
