The influenza virus NS1A binding protein gene modulates macrophages response to cytokines and phagocytic potential in inflammation

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.

Decoding the PITX2-controlled genetic network in atrial fibrillation

“…Among the genes with highest expression in CM1, we identified several atrial markers, including Nppa and Kcnj3, which are both associated with AF (30, 31) (Figure 2E). Genes enriched in CM2 included the L-type calcium channel Cacna1c, associated with sustained AF (32); Ablim1, which encodes an actin binding protein associated with left-right asymmetry and is expressed in the developing LA (33); Ivnsabp1, encoding an actin binding protein that functions in cytoskeleton stabilization (34); Fhl2, encoding a LIM-containing protein associated with adrenergic stress signaling (35); and Tacc2, a JCI Insight 2022;7(11):e158895 https://doi.org/10.1172/jci.insight.158895 centrosomal protein (36). For genes enriched in CM3, we identified several ion channels associated with AF and cardiac automaticity, including Hcn1, Cacna1d, and Slc24a2 (7,37).…”

Leveraging a neutrophil-derived PCD signature to predict and stratify patients with acute myocardial infarction: from AI prediction to biological interpretation

“…In mice with MAPK14 overexpression, the heart exhibits interstitial and perivascular fibrosis due to an increase in the number of myofibroblasts, whereas the absence of MAPK14 prevents cardiac fibroblasts from differentiating into myofibroblasts in response to ischemic injury, thereby hindering subsequent fibrosis [ 81 ]. Influenza Virus NS1A Binding Protein (IVNS1AB) encodes an actin-binding protein ND1 to prevent actin derangement [ 69 ], which plays a fundamental role in the locomotion and phagocytosis of neutrophils [ 82 ]. IVNS1AB overexpression in mouse hearts reduces cardiomyocyte apoptosis, protecting against doxorubicin-induced cardiomyopathy [ 83 ].…”