Surfactant lipids inhibit PI3K-dependent signaling pathways induced by IL-4 in alveolar macrophages

Abstract Alveolar macrophages (AMs) are less able to respond IL-4 in vivo than from the peritoneal cavity, due a still-unknown factor of lung environment. The aim this study is investigate whether surfactant lipids, which continuously endocytosed by AMs, could influence IL-4-mediated alternative activation and proliferation AMs. To that end, AMs were preincubated with lipids stimulated presence or absence protein SP-A, an amplifier actions. We found alveolar reduced IL-4- IL-4+SP-A-dependent arginase activity, expression genes associated activation, Mechanistically, decreased IL-4+SP-A-induced PI3K-Akt-mTORC1 signaling axis, but not IL-4-dependent STAT6 axis. Lipid-dependent inhibition Akt/mTORC1 axis consistent IL-4+SP-A-driven glycolysis mitochondrial respiration as well ATP citrate lyase histone acetylation IL-4. conclude inhibit PI3K-dependent pathways suggest decrease chronic diseases might augment fibrotic responses. This research funded Spanish Ministry Science Innovation through Grant PID2021-123044OB-I00 C. Casals