Abstract
Macrophages show remarkable phenotypic plasticity in response to environmental signals. Although it is generally less considered, cytoskeletal changes in macrophages influence their phenotype, including phagocytosis and secretion of soluble cytokines. Influenza virus NS1A-binding protein (Ivns1abp) belongs to the Kelch family of proteins that play a central role in actin cytoskeleton dynamics by directly associating with F-actin and by protecting against actin derangement. Due to its role in cytoskeleton preservation, the Ivns1abp gene might be a critical regulator of the macrophage phenotype and function under inflammatory conditions. In this study, we determine that the modulation of the Ivns1abp gene in macrophages could modify resistance to macrophages against inflammation and maintain functional phagocytosis. Our results indicate that inflammatory insults inhibit the Ivns1abp gene, whereby phagocytosis is inhibited and the ability of macrophages to induce proliferation and repair of damaged cells is compromised. Furthermore, our results show that inflammatory insults alter the activity of the transcription factor c-myc, a factor which directly modulates the expression of the Ivns1abp gene. In conclusion, this study demonstrates a central role of lvns1abp in promoting and preserving a reparative macrophage phenotype and resistance to this inflammatory environment.
Highlights
Macrophages exhibit a wide heterogeneity and functional plasticity, which is reflected in their expression of different phenotypes in response to microenvironmental signals
On the one hand, the Ivns1abp gene takes on an important role in both the coordination of actin cytoskeleton dynamics as well as cell shape and, on the other hand, modifications of the macrophage cytoskeleton can regulate their pro-inflammatory state versus the pro-healing active state, in this study we investigated the contribution of the Ivns1abp gene in the control of the actin cytoskeleton of macrophages during inflammation and the role of this gene in macrophage polarization
Modulation of Ivns1abp gene in macrophages increases the resistance against inflammation and cytoskeleton derangement provoked by cytokines
Summary
Macrophages exhibit a wide heterogeneity and functional plasticity, which is reflected in their expression of different phenotypes in response to microenvironmental signals. We tested the reparative capacity of macrophage supernatants using a cellular scratch model (Fig. 2a), and second, we determined the ability to induce proliferation by enhancing Ki-67 and PCNA mRNA expression in a co-culture with renal epithelial cells (Fig. 2b).
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